Post by tomsylver on Nov 8, 2017 7:42:37 GMT
TESARO's (TSRO) CEO Leon Moulder on Q3 2017 Results - Earnings Call Transcript
November 07, 2017, 16:15 ET
Executives
Jennifer Davis - VP of Corporate Communications & IR
Timothy Pearson - CFO and EVP
Leon Moulder - Co-Founder, CEO and Director
Mary Hedley - Co-Founder, President, COO and Director
Analysts
Tazeen Ahmad - Bank of America Merrill Lynch
Yanan Zhu - Wells Fargo Securities
Kennen MacKay - RBC Capital Markets
James Birchenough - Wells Fargo Securities
Charles Butler - Guggenheim Securities
Seamus Fernandez - Leerink Partners
K. Choi - Barclays PLC
Peter Lawson - SunTrust Robinson Humphrey
Steven Breazzano - Evercore ISI
Operator
Welcome to TESARO Third Quarter 2017 Conference Call. As a reminder, this call is being recorded and webcast. I'll now turn the call over to Jennifer Davis, Vice President of Investor Relations and Corporate Communications at TESARO. Please go ahead.
Jennifer Davis
Thank you, Nicole. Good afternoon, and thank you for joining us today to discuss our recent business progress and TESARO's third quarter 2017 operating results. With me here today are our CEO, Lonnie Mulder; our President and COO, Dr. Mary Hedley; and our CFO, Tim Pearson.
Earlier this afternoon, we issued a news release detailing our Q3 results. Please note that this news release and the slide presentation that we'll refer to during this conference call are both available in the Investors section of our website, www.tesarobio.com.
Before we begin, I'd like to remind you that discussions during this conference call will include forward-looking statements. These statements are subject to a number of risks and uncertainties that could cause our actual results to differ materially from those described in these forward-looking statements. We undertake no obligation to update or revise any forward-looking statements for any reason. The factors that could cause actual results to differ are discussed in the press release issued today and in our SEC filings, including our annual report on Form 10-K for the year ended December 31, 2016, and our quarterly report on Form 10-Q for the quarter ended June 30, 2017.
During today's call, we may refer to certain non-GAAP financial measures that involve certain non-GAAP figures. These non-GAAP financial measures are not a substitute for GAAP financial measures and are unlikely to be comparable to non-GAAP information provided by other companies. We believe non-GAAP measures may be useful to investors as a supplement to, but not as a substitute for, the applicable GAAP number. I'd now like to turn the call over to Lonnie Moulder, CEO of TESARO. Lonnie?
Leon Moulder
Thank you, Jen, thank you, everyone for joining us this afternoon. TESARO had an excellent quarter, marked by the successful launch of ZEJULA in the U.S, the positive CHMP opinion received for ZEJULA in Europe and progress on multiple fronts across our clinical development portfolio. Our first international launch, VARUBI oral is underway in Europe and we're well to prepared for 2 additional product launches before year-end, VARUBI IV in the U.S. and ZEJULA in Europe. The opportunities for ZEJULA to benefit patients extends well beyond ovarian cancer. And as Mary Lynn will describe today, we are prepared to initiate several Phase III trials in ovarian, lung and breast cancer to expand the ZEJULA franchise.
Our immune-oncology portfolio continues to rapidly advance and we now have 3 antibodies in the clinic targeting key immune checkpoints. We are rapidly advancing our registration trial of TSR-042, our anti-PD-1 antibody and our first IO/IO combination trial evaluating TSR-042, plus TSR-022, our anti-TIM-3 antibody is now enrolling patients.
I'd like to discuss the U.S. ZEJULA launch, which is off to a very strong start. The unsurpassed and compelling efficacy in ZEJULA as demonstrated in the NOVA Phase III study, combined with a, well-executed commercial strategy has produced a paradigm shift in the treatment of women with recurrent ovarian cancer, such that maintenance treatment with ZEJULA has quickly become a new standard of care. Following the introduction of ZEJULA, the number of women to resort to watchful waiting has declined remarkably. In addition to communicating the unsurpassed efficacy of ZEJULA in a broad patient population as demonstrated in the NOVA trial, our field force is effectively communicating a simple, elegant marketing message that resonates with clinicians. More time for more women.
During the third quarter, we experienced impressive growth in both the number of patients treated with ZEJULA as well as in the number of prescribing physicians. In September alone, approximately 2,500 patients were treated with ZEJULA and since approval, more than 1,700 unique healthcare providers had written a prescription for ZEJULA, including over 650 new prescribers in the third quarter. Utilization of ZEJULA has been evenly divided among patients with and without bracket BRCA mutations, and prescribers are about evenly split between community clinics and hospitals, both academic and community. Most new patients have started ZEJULA treatment at the 300 milligram dose and as expected, the average dose per prescription refills has moved towards 200 milligrams as physicians individualize the dose for their patients in a manner similar to what was observed in the NOVA trial. While still early in the launch, the duration of patient therapy is generally in line with our expectations. Noting that during the first weeks of product availability, some patients receiving ZEJULA -- received ZEJULA for later line treatment or began treatment after a prolonged platinum-free period while in response to platinum. Of course, durations of therapy in these patients would be shorter than for most patients who more closely represent the NOVA population.
Reimbursements coverage for ZEJULA is excellent, with more than 99% of life cover for ZEJULA across Medicare, Medicaid and private insurance. Approximately 60% of patients treated with ZEJULA had commercial insurance coverage and about 1/3 are covered by Medicare. Utilization of our patient assistance programs increased slightly from what was observed in the first quarter of launch and landed within the range of 25% to 30% of total unit volume, in line with other highly successful oral oncology products. The majority of patients assistance volume consists of patients who are unable to pay for the Medicare part [indiscernible] and who are impacted by the lack of nonprofit foundation assistance. In accordance with our mission, we've assigned our patient support programs to be appropriately comprehensive. We believe these programs are in the best interest of patients and support our belief that providers should choose ZEJULA as the preferred part inhibitor for recurrent ovarian cancer patients, who can benefit from maintenance treatment regardless of their ability to pay.
ZEJULA sales exceeded $39 million in the third quarter. And in September, ZEJULA captured approximately 60% of the U.S. part inhibitor market among patients with ovarian cancer, despite the recent label expansion of a competing product in the maintenance study. For comparison, in the first 6 weeks of availability, following launches, of the 2-part inhibitors indicated for maintenance treatment, approximately 4 times as many patients initiated treatment with ZEJULA as those who started maintenance treatment with the most recently approved part inhibitor in the comparable time period. Unsurpassed efficacy, convenient once daily dosing that easily adjusted to manage tolerability and a well-executed strategy has positioned ZEJULA to continue to be the market leader.
In Europe, strong uptake of our extended access or EIP -- EAP program continues. More than 350 patients have been treated to-date, with the largest participation occurring in Germany and the U.K, the number 1 and number 4 markets in Europe, respectively. Approximately 100 TESARO associates in Europe are actively engaged in prelaunch activities, and a European Commission approval of ZEJULA. This launch will begin in Germany, with subsequent launches in the U.K, Nordics and additional countries throughout 2018. The European comparative dynamic is highly favorable for ZEJULA. This single approved part inhibitor in Europe is indicated for maintenance treatment, which has provided a foundation for the maintenance paradigm in recurrent ovarian cancer, however, it is narrowly indicated for the minority of patients who harbor a BRCA mutation and is saddled with an unusually burdensome dosing regimen. By comparison, ZEJULA will launch as the only once daily part inhibitor for maintenance treatment, regardless of BRCA mutation status. We look forward to updating you on the launch next year.
2 weeks ago, the FDA approved VARUBI IV and we plan to launch this important product this month. VARUBI IV will provide clinicians with convenient, ready-to-use formulation in a ready-to-use infused bottle format without need for reconstitution or refrigeration. As a result, utilization and busy chemotherapy clinics is straightforward and easily adopted into existing practice patterns for administration of anti-medic regimens associated with chemotherapy. VARUBI IV is not only meaningful for patients, it is designed to address the needs of pharmacists and nurses who seek efficiencies and prefer not to spend staff time and resources reconstituting and mixing IV solutions, some of which are continually in short supply as required for the preparation and administration of the other IV and K-1 products. Importantly, with a total market opportunity consisting of 3 to 4 million doses per year, or nearly $1 billion annually, we believe VARUBI IV can be a substantial product for TESARO, serving as an efficient cash generator to support the development of our compelling and potentially transformational pipeline development programs. The IV formulation of VARUBI will enable us to reach the majority of the U.S. CIMB market and over time, extend the use of NK-1 receptor antagonists to the majority of patients receiving chemotherapy regimens including cisplatin, carboplatin and anthracycline cyclophosphamide combinations as recommended by the NCCN and ASCO guidelines. With that, I will now turn the call over to our CFO, Tim Pearson, for a review of our third quarter financial results. Tim?
Timothy Pearson
Thanks, Lenny. For the third quarter of 2017, TESARO reported total revenue of $142.8 million compared to $17 million for the third quarter of 2016. Net product revenue totaled $41.8 million for the third quarter of 2017 compared to $1.3 million for the third quarter of 2016. This growth was driven by the continued strong launch of ZEJULA in the U.S. ZEJULA net revenue totaled $39.4 million for the third quarter. Revenue from ZEJULA sales is recorded net of estimated discounts, returns, charge backs, rebates, co-pay assistance and other allowances. These gross to net adjustments represented approximately 10% of gross ZEJULA product sales for the third quarter. ZEJULA demand shipments from special distributors and specialty pharmacies increased sequentially by 87% for the third quarter compared to the second quarter this year. In the third quarter, approximately 65% of prescriptions were filled through our specialty pharmacy channel and the remainder were filled by specialty distributors.
VARUBI net revenue totaled $2.4 million for the third quarter compared to $1.3 million for the third quarter of 2016. As Lonnie said, we look forward to bringing our IV formulation of VARUBI to U.S. customers this month, which will enable us to reach the largest segment by far of the CINV market. License collaboration and other revenue totaled $101 million for the third quarter of 2017 compared to $15.7 million in Q3 2016. And included the $100 million upfront payment received as part of our Takeda license agreement.
Research and development expenses increased to $73.4 million for the third quarter compared to $60.8 million in Q3 of 2016. This increase was primarily driven by higher headcount, the advancement of our early-stage immune-oncology portfolio and expansion of the TSR-042 and TSR-022 programs. Selling, general and administrative expenses increased to $84 million for the third quarter compared to $37.7 million in Q3 of 2016. This is primarily due to increased headcount and other personnel related costs, activities in support of the launches of VARUBI and ZEJULA in the U.S. and Europe and higher professional service fees.
For Q3 2017, TESARO reported a net loss of $25.3 million compared to a net loss of $87.9 million for the third quarter of 2016. As of September 30, 2017, TESARO had approximately $521.3 million in cash and cash equivalents. This balance reflects operating cash utilization during the third quarter of approximately $94 million, excluding the $100 million upfront payment received as part of the Takeda license agreement. Looking ahead, we expect that our cash and cash equivalent balance will decrease by approximately $110 million to $120 million during the fourth quarter of 2017, excluding a $15 million milestone that we anticipate paying upon approval of ZEJULA in Europe.
With regard to ZEJULA, we expect net revenues of between $105 million and $115 million for the full year 2017. With the launch of the VARUBI IV, we expect to ship product at the end of this month and through December. The shipments will primarily be orders from providers taking advantage of launch discounts. Our ability to recognize those orders as revenue will depend on many factors and could be subject to constraint. At this time, we believe that only a portion of shipments will be recognized in the fourth quarter, but that will be determined at a later time. Our best estimate for IV revenue for the fourth quarter is in the range of mid-single digit millions of dollars. Additional guidance may be provided later in 2018 after we have established a demand pattern. With that, I'll hand the call over to Mary Lynn for an update on our development programs.
Mary Hedley
Thank you, Tim. Over the last year, the development pipeline has delivered 3 product approvals and we anticipate a fourth this month based on a positive CHMP opinion issued in September for the maintenance treatment of women with recurrent ovarian cancer following a response to platinum. With this approval in hand, we intend to launch ZEJULA in Europe before years end. So gratified by the success of our ongoing launch and the use of ZEJULA to meet the needs of women with recurrent ovarian cancer, we must and will do more. We intend for women across the full spectrum of ovarian cancer to benefit from ZEJULA, including those who are newly diagnosed. Patients with newly diagnosed ovarian cancer receive a standard regiment that includes surgery followed by six cycles of chemotherapy.
Subsequent to completion of chemotherapy, they are most often subjected to a watch and wait approach, but nearly 85% of those with advanced disease will experience a recurrence. We believe the treatment benefits of [indiscernible] immunotherapy can expand to this first-line maintenance study. And in so doing, provide even more time with for this large patient population, with limited or no other treatment options. We are effecting this possibility with the ongoing Phase III PRIMA study, where in the PFS benefit from niraparib treatment versus placebo control will be determined in patients with newly diagnosed stage III/IV ovarian cancer. Stratification factors for this study include the homologous recombination deficiency or HRD status of the tumor and the primary endpoint analysis will include a hierarchical step down for PFS, first in patients with HRD-positive tumors and just a result statistically significant than in the entire patient population.
And given a very robust enrollment rate in the study and our desire to gather clinical biomarker data that can be used to strengthen our competitive position in ovarian and other tumor types, we intend to expand this study from 330 to 468 patients. Despite the expansion, we continue to expect the enrollment will complete in the first part of next year and will be followed by data readout in 2019.
We are all aware that immunotherapy with anti-PD-1 antibodies has thus far offered unprecedented duration of clinical benefit across the large number of tumor studies. However, to date, women with ovarian cancer have proven relatively nonresponsive to this approach. We believe the addition of niraparib to our own anti-PD-1 antibody, TSR-042, could enable these women to experience the durable remissions provided by immunotherapy treatment. Our new Phase III frontline maintenance trial, first, has been agreed with major study groups and will initiate in the first half of next year, following completion of the ongoing clinical tolerability assessment of the TSR-042 and niraparib combination.
In Europe, newly diagnosed patients with ovarian cancer can receive the bevacizumab in combination with chemotherapy. And use bevacizumab in this study is now under review by FDA. Based upon the AVA NOVA data set, we believe a combination of bevacizumab and niraparib could provide compelling advancements for women in the front line setting. Next month, we expected dose a first patient in OVARIO, a Phase II study of niraparib in combination with bevacizumab in patients with newly diagnosed ovarian cancer. And we anticipate results from this study to be available in 2019.
For patients with recurrent ovarian cancer, we continue to explore the monotherapy benefit of ZEJULA in the ongoing QUADRA study and will supplement these efforts with our combination studies. Our success with the ZEJULA launch and interactions with practicing physicians has taught us the commercial value of avoiding, if possible, the use of complex tumor-based biomarker testing in the ovarian cancer Lateline treatment setting. Therefore, to optimize the differentiation and commercial opportunity of the QUADRA data set, prior to analyzing the response data, we are exploring the potential use of a blood-based biomarker to define a patient population which might best benefit from niraparib treatment. For this reason, data readout for QUADRA will likely be in Q1 of next year. Efforts to further lengthen niraparib treatment benefits for women with recurrent ovarian cancer will be via two approaches, a chemotherapy free bevacizumab combination and an IO combination with anti-PD-1 therapy. A chemotherapy free regimen for women who responded for at least 6 months to frontline platinum therapy has shown promise in the AVANOVA trial. AVANOVA conducted by our ENGOT collaborators is evaluating the combination of niraparib plus bevacizumab in patients with recurrent ovarian cancer. At ESMO, updated data was presented for part 1 of the study and demonstrated preliminary evidence of activity, with a median progression free survival of 49 weeks and an expected and manageable adverse event profile. We are encouraged by these early results and the potential for these 2 drugs in combination. The ongoing Phase II portion of this study in which patients are randomized to niraparib versus bevacizumab plus niraparib is ongoing and the trial is anticipated to complete enrollment this year, with data anticipated next year.
For those women with recurrent ovarian cancer whose last response to platinum was less than 6 months, we continue to advance TOPACIO, a clinical study of niraparib and an anti-PD-1 antibody. Patients with triple negative breast cancer are also being evaluated in this study. These tumors typically show relatively low response rates to anti-PD-1 antibody and PARP inhibitor monotherapy. And we hope to improve upon the clinical activity with this combination approach. Early data from TOPACIO was presented at ESMO in September. At the time of data presentation, 37% of platinum-resistant ovarian cancer patients and 44% of triple negative breast cancer patients remained on study treatment. And for patients with a PR or CR, most were continuing study treatment, further pointing to what is most important, durability of the response. We expect clarity around a potential registration study and additional data from this trial to become available in the first half of next year.
We see promise for niraparib that extends beyond ovarian cancer. Given the gene expansion deficiencies in patient with lung cancer, this tumor type is of particular interest as a potential opportunity for niraparib treatment. A large number of these patients have reduced expression of genes involved in DNA repair pathways, a higher rate of homologous recombination deficiency and platinum responsiveness. All hallmarks of sensitivity to PARP inhibition. Anti-PD-1 antibodies are approved for use in this setting. And based on TOPACIO and other data, may be effectively used in combination with the niraparib. Clinical studies are now ongoing, with the goal to assess the potential of niraparib and TSR-042 monotherapies as well as TSR-042 and niraparib combination therapy to provide benefit in this tumor setting. The studies will be used to define monotherapy disease control rate for each agent in patients with lung cancer, gather biomarker data and ultimately establish how vulnerability the preliminary activity of the niraparib plus TSR-042 combination, all to support our anticipated Phase III niraparib and TSR-042 lung study, which we will -- we expect will begin enrolling patients in the fourth quarter of 2018. More details on these studies will be provided at an appropriate time such that we can continue to maximize any competitive advantage in the space.
Our immuno-oncology programs remain on target with specific data results next year. Our current pipeline includes antibodies directed to PD-1, TIM-3 and LAG-3 and a bispecific to PD-1/LAG-3.
Beginning with TSR-042, our anti-PD-1 antibody. Patients with metastatic microsatellite instability high or MSI-high tumors, continue to enroll in the expansion phase of the ongoing GARNET study and receive a fixed dose of TSR-042 4 times, once every 3 weeks followed by administration every 6 weeks until disease progression. As previously discussed, we intend to use this study to support registration of TSR-042 in patients with MSI-high cancers and have agreed with FDA on this strategy. The primary efficacy in this trial are overall response rate and duration of response. At ESMO at September preliminary safety, efficacy, receptor occupancy and pharmacokinetic data for TSR-042 was presented, which indicated that TSR-042 has a safety and efficacy profile expected for an agent targeting the PD-1 pathway. We expect to share additional efficacy data from our expansion phase of this study in the second half of next year.
As you are aware, while anti-PD-1 therapy has proven effective in multiple tumor types, the response rates are typically low for any given unselected patient population. Many mechanisms are likely responsible for this observation, including an immunosuppressive tumor microenvironment brought about by the concerted actions of regulatory T cells, macrophages, [indiscernible] cells and the tumors themselves. The results, an effected T-cell population that is incapacitated and therefore, unable to sustain itself or it's ability to deal a definitive lethal blow to tumor cells. In the presence of a tumor-reactive effector T-cell population, continued support by the microenvironment is essential to retain maximum T-cell mediated killing. TIM-3 is expressed by multiple immune cells and intracellular signaling via TIM-3, dampens immune-mediated tumor cells on multiple fronts. TIM-3 ligand engagement causes the production of immunosuppressive molecules by regulatory T cells and then [indiscernible] cells and is a dominant negative signal in T-effector cells. Such that, even in the presence of anti-PD-1, these cells are not fully activated. Thus, blockade of TIM-3 expected to have multiple positive effects in the tumor microenvironment, including restoration of T-effector cell activity.
TSR-022 is our anti-TIM-3 antibody. Initial data from the dose escalation stage of our Phase I study of TSR-022 will be presented in the upcoming SITC meeting later this week. At the highest dose 10 mg [ph], several patients are still receiving treatment. And we anticipate that any clinical benefit derived from monotherapy treatment will be further enhanced by use of anti-TIM-3 in combination with TSR-042. A combination trial of TSR-022 plus TSR-042 at fixed doses of each antibody continues to enroll patients. The ongoing combination study will initially provide data to effect tolerability and identify the appropriate dose of TSR-022 to use in combination with TSR-042. And following this will be expanded to access activity in a cohort specific to patients with anti-PD-1 responsive tumors who are naïve to treatments and the cohort specific to patients with anti-PD-1 resistant tumor type. We look forward to showing initial data from this combination next year.
LAG-3 is also effect by effector T cells and is in part responsible for their inadequate antitumor response. While anti-LAG-3 has been shown to potentiate the effect of anti-PD-1 therapy in nonclinical and clinical studies, the most significant step forward may be recognized with the triple of combinations. Multiple nonclinical studies and different investigators including ourselves have demonstrated that a triplet is more effective than a doublet combinations of anti-PD-1 with anti-LAG-3 or anti-TIM-3 at causing tumor shrinkage regressions. And experiments using humanlike mice in a human tumor model, a combination of TSR-022, 042 and 033 was most effective at inhibiting tumor growth. In addition to the ongoing clinical studies with TSR-042 and TSR-022, TSR-033 our anti-LAG-3 antibody is well into a dose escalation Phase I clinical trial, utilizing a flat dose schedule. And combination studies with TSR-042 should initiate in a couple of months. The dose escalation phase of this study is enrolling all comers, and once the TSR-033 dose is identified to combine with TSR-042, cohorts will be instructed -- restricted to patient populations that are expected to benefit from the combination approach. The utilization of a flat dose and rapid expansion in the combination cohort will shorten the development timeline so that we are positioned to best optimize the combination approaches for our IO assets well into the future. And with that, I'll turn the call back over to Lonnie. Lonnie?
Leon Moulder
Thank you, Mary Lynn. Operator, this point, can we please open the call for questions?
Question-and-Answer Session
Operator
[Operator Instructions]. Our first question comes from the line of Robyn Karnauskas with Citigroup.
Unidentified Analyst
This is Krip [ph] on for Robyn. I just had a couple of questions about real world experience with ZEJULA. First question is about safety. Can you talk a little bit about how -- what sort of safety issues you've seen with patients, how doctors are managing, and any color on rates of discontinuation that you're seeing? And also can you talk a little bit about genetic test requirement. Are doctors requiring the genetic test even before residual or since it's been approved with a broad label, it seems like it's unnecessary?
Leon Moulder
Sure, and thanks for the question. I'll answer the first question first. There are no requirements related to genetic testing. The ZEJULA prescriptions are written for patients with recurrent ovarian cancer and 99% coverage across all areas including Medicare, Medicaid and commercial insurance. And obviously, that's what's allowed us to rapidly penetrate this market. So no genetic testing involved whatsoever. As far as the real world experience, it's actually quite similar to the NOVA study. So as you all know, if you look at the Phase III studies of PARP inhibitors in the recurrent ovarian cancer setting, all 3 agents had discontinuation rates in the 10% to 15% range. All 3 of them following the 10% to 15% range.
Some of the agents have a higher level of constitutional side effects. Things that patients feel. We believe we're better positioned than the other PARP inhibitors, with regards to those types of side effects. The one side effect that people point to that we've recognized relates to model suppression, again, something that all PARP inhibitors have. But ZEJULA actually has a higher incidence of thrombocytopenia. So grade 3, grade 4 thrombocytopenia was observed in the NOVA trial. And as you all know, what was reported is after cycle 2, the instance of grade 3, grade 4 of thrombocytopenia dropped to 1 or less percent. And the total amount of discontinuation in the NOVA trial related to thrombocytopenia was only 3%. So taking the experience from NOVA and understanding how thrombocytopenia should be managed, we established a communication and education program around our launch.
And what does that consist of? That ensures that physicians and nurses understand as patients receive their standard CBC blood test, to look at platelets and to expect, in the first cycle, approximately half of the patients will have a dose delay and move from the 30 -- 300 milligrams to the 200milligram, as per the NOVA study. And in the second cycle, additional patients will be dose adjusted. So what we do in the first 2 cycles, we ensure that clinicians know how to tailor the dose to that patients needs. We do that with our field force, with our oncology nurse educators who are informed whenever a prescription is written and with our specialty pharmacy partners who then call the patient on a weekly basis to establish a relationship and call the actual prescribing office. And in doing this, what we have found, as I described earlier, is that most of the prescriptions started 300 milligrams and the refills are now headed towards 200 milligrams.
So we would expect, as we said at the time of launch, that the average dose will be 200 milligrams, the most common dose will be 200 milligrams and that's really what we're seeing. From discontinuation rate, we're not seeing anything at all different than what was observed in the NOVA data. And as you can tell by the uptick on the drug, there are 4 times as many patients receiving ZEJULA and the benefits of ZEJULA, than patients who've been prescribing either of the other 2 PARP inhibitors. So I think the NOVA study taught us quite a bit and we have taken that message and that education to the clinicians. And although, ZEJULA's associated with a higher incidence of thrombocytopenia, the clinical sequelae are not at all unanticipated and no different than what was seen in the NOVA study. So we're keeping our patients safe. And we are ensuring that they are on a regiment that will lead to the benefits that we would expect them to receive, regardless of the dose they land on as observed in the NOVA study.
Unidentified Analyst
Great. That's very helpful. If I can just keep taking a follow-up question to the genetic test. Now since they're not doing a genetic test, is there anyway you guys can follow how the responses in HRD-negative patients is in the real world?
Mary Hedley
Not really, because they are not, again, doing the test.
Operator
Our next question comes from the line of Tazeen Ahmad of Bank of America.
Tazeen Ahmad
Maybe the first one on when we could potentially want to see some data from your non-small cell lung study that you are about to do. Whether it be interim or full data set? And then a question on TOPACIO. You told us in your press release that you were going to give us another update on the first of '18. Just wondering does that include longer follow ups for the patients that we were shown at ESMO? And if that would also include additional patients? And then I have one more follow-up?
Mary Hedley
Yes, so thank you for your question, Tazeen. The long trial data won't be available until probably in the middle of 2018. And again, that's preliminary data based on, first of all trying to understand the efficacy and safety in the immunotherapy study for each of the agents and then ultimately in combination. As it relates to TOPACIO, we anticipate yes, that you will see follow-up data from the patients that you saw at ESMO, in addition to several patients who didn't even have response rate data yet at ESMO.
Yanan Zhu
And is that likely an ASCO presentation?
Mary Hedley
That would be a reasonable expectation. I mean, I can't promise that, obviously.
Yanan Zhu
Right. Thanks. Then last question would be on the QUADRA study. When are you expecting results for that?
Mary Hedley
In Q1.
Operator
Our next question come from the line of Kennen McKay of RBC.
Kennen MacKay
Lonnie, maybe one for you. It seems like your marketing strategy for IV VARUBI changed historically from it being focused on contracting to one potentially taking advantage of some of the factors involved in the preparation of IV VARUBI versus IV amends. Can you maybe talk about the changes in the strategy there a little bit more?
Leon Moulder
Yes, so we are always enthusiastic about the design of the formulation because it is so easy. It's a little 100 milliliter bottle and it's already formulated. You just attach the IV line, there's actually a little hook already on the bottle so you then turn it upside down and put it on the IV pole and then infuse it in the patient in approximately 30 minutes within 2 hours of the chemotherapy. And we thought that was quite elegant, practical. As an old hospital pharmacist I just love it. But what's happen most recently is we've been -- we've had a large additional orders of oral VARUBI in centers that have been IV immense centers. And we investigated that and determined that what was being faced by many of these hospital pharmacies and clinic pharmacies was a shortage of sternal intravenous solutions for mixing drugs that come lyophilized or need to be diluted.
And the current IV participant is one of those drugs. You have to first dilute it in a vial, shake it after a while, then you have to get an IV bag and there's intermittent shortage of those, both Celine and dextrose, D5W and you in that bag then you have to refrigerate it until you get it to the patient. And watching all that happen and listening and doing some more qualitative market research, it became obvious that to us that there is a need that our elegant formulation matches really well. So it's sort of like a perfect storm that's taken place and we're leveraging that. So that's the fine-tuning of the strategy you are referring to Kennen.
Kennen MacKay
That's it. That's really helpful. And then just had a quick question on some of the guidance around the size of this market and one for Tim on potential guidance for ZEJULA. So just getting back to the size of the potential CINV market here. Regarding that sort of $1 billion potential, it seems like IV amends is sort of on a $550 million-ish run rate now. And so I was just wondering sort of what gets it up to that $1 billion market. The patient currently aren't being treated or again, sort of volume or maybe some additions on sort of the pricing growth or what should we be thinking about?
Leon Moulder
Excellent question, it's the former. It's really the percentage of patients who actually under both ASCO and NCCN guidelines, patients receiving platinum, carboplatinum cisplatin or women with breast cancer receiving AC recycle cyclophosphamide regimens, who were not receiving an NK-1. And we know from the Phase III studies of all of the NK-1 receptor antagonists, when you give the best care 5HT3 receptor antagonists in dexamethasone, 30% to 50% of those patients still go home, they vomit, they required rescue medication, they return to their clinics for hydration, they report to emergency rooms for hydration and for admissions. So that -- I mean, there's a reason why ASCO and NCCN says all those patients need to receive an NK-1. So it's now our job, with I think this opportunity with this formulation and our field force in our educational initiatives to actually maximize the opportunity for the whole class. So the class itself could be utilized 2 to 3 times more than it is today, under the guidelines. And that's why we size the opportunity being as large as $1 billion.
Kennen MacKay
That's it. Okay. And if I can just squeeze in one more maybe for Tim. I just wanted to make sure that 2017 guidance for ZEJULA right. I've heard of $105 million to $117 million. And if I did, it seems like on the lower end of that, that's not implying much quarter-over-quarter growth there. So just wanted to see if that was taking sort of an ultraconservative stance or is that was relating to anything new in the dynamics of [indiscernible] approval expansion?
Leon Moulder
Let me just comment on the reports was in turn it over to Tim. It's not at all related to the importance, we have via the IMS data. What they've done in the first 6 weeks of their launch, a few hundred patients, in addition to their normal baseline, which is 1/4 of what we obtained. And their growth actually, if you look at the intrinsic data, a substantial part of that relates to G BRCA breast cancer, not even on the ovarian study. So we're not seeing a lot of traction there on their behalf. And obviously, we had, if you recall, last time we talked about how we were going to do this year, we said something greater than 100, and now we have a range that I'll refer to Tim. Tim?
Timothy Pearson
Ronnie, the range that we quoted was $105 million to $115 million for the full year for ZEJULA.
Operator
And our next question comes from the line of Jim Birchenough of Wells Fargo Securities.
James Birchenough
So I guess on the 60% market share for ZEJULA, how sticky do you think that market share is? And maybe you could delve into what gives you the dominant market share and if you think you can maintain it? And related to that, whether contracting you think will be an important part of maintaining market share and whether over time you think you're going to get close to the discounted price maintaining that share, do you really think it's taking with the existing profile?
Timothy Pearson
Thanks for the question, Jim. As far as the market share, we talked about the market share on our second quarter. And from that point in time, which was June 30, to September, it's ticked up a couple of percentage points and that's in the face of [indiscernible]. So obviously, we're quite encouraged by that. The confirming we are getting good feedback from nurses, from support groups and obviously from physicians. And looking at any category of pharmaceuticals, the first to launch, the initial land grab as I say, is ours. So now that there are with an additional product and sometime next year a third product, how would those typically perform based on the fact that our data is unsurpassed. Our convenience is best and the value proposition we have relative to our 300, 200, 100 milligram dosing and pricing. How is it that they will take market share? Obviously, they'll get some share but the first to launch that's established itself this well, typically retains the largest market share.
So I would see stickiness. I'm not going to predict a specific market share that we're going to have long term. But I think there's enough analogs out there you can get a sense of the range of what that would be. So I guess that's how I would summarize where we are. Now going forward, of course, we have 175 people in the field across sales, account management, medical science liaisons, college nurse educators, providing solutions people. And share a voice and that is as strong as any large pharma or combination of live and work market and AstraZeneca would want to dedicate from their sales forces into ovarian cancer. So we're confident we are putting the right personnel resources in place. And then overall financial support of advertising and performance on medical education, our -- no, actually leaning towards the high end. So we think we'll be able to contingent -- continue to effectively compete, regardless of a change in the market dynamics based on the commitments we've made but importantly, how the product performs. And the data sets we've generated to date.
James Birchenough
And Lonnie, if I could just our follow-up for political of market expansion here. We have a sense of what proportion of patients that are eligible for second line maintenance receiving it right now? And are using any of the label uses for front line maintenance
Leon Moulder
Yes, so for all of the PARP inhibitors until this recent greater use in breast cancer for LYNPARZA, the ovarian use has been around 90%. The ovarian covers peroneal and fallopian tube. I guess -- I think, we're a little over 90% actually. Within ovarian, this is where it gets interesting [indiscernible] express out differently if you look at the different categories. First line maintenance, recurrent maintenance, early line treatment, late line treatment. The largest portion of our use, of course, is in recurrent maintenance. There is some late line treatment and there's also some first line maintenance with our drug. We have a mix. But the largest portion again is recurrent maintenance. And obviously, that is what we promote. That is what we educate on.
I'm just giving you a sense what's happening out there. So when you think about the market opportunity whether you look at the U.S. or Europe, there is about markets in Europe that we are targeting, they're about 10,000 patients that can benefit annually in each of the markets. So 20,000 in total. So about 10,000. If we just do the simple arithmetic on this, each week somewhere between 180 and 200 new patients become eligible because they're now in response to platinum, when you define the recurrent ovarian cancer markets. So if you look at our uptick today, you would say, we've had really nice penetration into that. We do get use elsewhere. But there's still another -- there's probably maybe 3 times as many patients, at least in the maintenance study that can be obtained as we continued on our launch trajectory. When you look at each pool of patients available on a weekly basis going forward. Does that make sense?
James Birchenough
That's really helpful. And maybe one final one from for Mary Lynn and that's just from TOPACIO, any reason why we won't see an update in San Antonio Breast Cancer symposium? And then on prospects for accelerated approval, do you have a sense of how many patients might be required and if that's a legitimate path?
Mary Hedley
So you won't see an update at San Antonio because the distance or duration of time between ESMO and San Antonio is really too short for us truly provide a meaningful update. So any updates that will happen will happen in the first half of next year and if that time will also define what the registration strategy will be for the combination approach. And we're thinking just based historically and with patients what we've seen from FDA, anywhere between 60 and 100 patients could be appropriate for an accelerated approval strategy.
Operator
Our next question comes from the line of Tony Butler of Guggenheim Security.
Charles Butler
Mary Lynn, just curious about the PD-1 strategy and the combinations. And I'm asking, if you combine 22 and/or 33 with 42 so PD-1 TIM-3 or LAG-3. And you're dosing at Q3 intervals and then move to Q6, the question is, what's the dose of the second combination agent? Does it also change? And then the second question is around they tell that has been presented before on T-cell exhaustion with one of the combination and I'm curious if, in fact, you might actually move forward in an IO refractory setting with the combo of a PD-1 plus 1 of the 2 other agents?
Mary Hedley
Sure, so that's a good question, Tony, the schedules. So we designed the scheduled 042 to be flexible to accommodate potential IO combinations or potential chemotherapy combinations given on a Q3 week or moving to Q6 week schedule. So as most of those other agents -- most of those chemotherapies are administered on a Q3 week basis, this would fit nicely with that. We would administer the chemotherapy at week 036 then you'd administer 042 at week 03 and then 6. And then as you progress further, you would just skip. Every chemo, every -- sorry, every third week you would be getting chemo, but every 6 week you would be getting chemo plus 042.
So it still fits nicely into the schedule. As we think about combining with 022 and 033, right now, we're thinking of maintaining a Q3 week schedule and we'll see during the combination will actually during the monotherapy and then the combinations, if we can move those agents to Q6 week as well. But right now, it's too early to predict that. And then related to your question on an IO refractory patient population, I'm going to assume by that question and correct me if I'm wrong, you mean tumor types that don't respond to PD-1 therapy, generally speaking. And yes, the intent is ultimately to also include those types of patients, because what we see from our tumor profiling experiments where we take fresh human tumors and look at tumor microenvironment, we see that even in a refractory -- even in tumor types that are refractory PD-1 therapy they do have T cells.
And in fact, there is a high level of TIM-3 and/or LAG-3 on those T cells in combination with PD-1. And we know that once those T cells express TIM-3 or LAG-3, a PD-1 antibody will not be sufficient to fully reactivate them so you really do need the combination therapy. So it is certainly one hypothesis as to why we don't see responses in certain tumor types such as, for example, call it to PD-1 therapy alone.
Charles Butler
And Mary Lynn, last question really on the same topic is, I'm really referring to -- also referring to IO refractory patients who can previously treated with an anti-PD-1 and for whatever reason it no longer has demonstrated regression of the tumor?
Mary Hedley
Yes, so we typically use the term resistant. So they have acquired resistance to PD-1 therapy meaning like a long our original melanoma patients that wasn't originally responding that is now progressed or has demonstrated progression on Petro Citi scanning following PD-1 therapy. So yes, we are actually including those patients. We will be turning them an expansion cohort and actually including them right now in our combination studies.
Operator
Our next question comes from the line of Ms. Seamus Fernandez of Leerink.
Seamus Fernandez
Maybe a couple of -- Lonnie, can you help us understand the context of VARUBI, when we can be confident that flow rates for both oral and IV VARUBI are likely to be booked as revenue and then we can sort of have a better understanding of where we are at a consistent run rate with regard to VARUBI? The second question is, as we think about the introduction of potential introduction of first-line and obviously the availability of second line of Astin plus chemo, can you just help us understand how you think that will actually affect the market for PARP maintenance? I think you can see 2 possibilities, you drag more patients into response and then actually expand the patient population. Or perhaps, alternatively, it could be viewed as not part of the regimens. I would just love to know how you're thinking about that. And the last question is, as we think about the opportunity for the other IO agents and your TIM-3 antibody, can you just give us a general sense of the number of patients? I think the abstract says 31 patients were treated. But in terms of the number of patients where we we'll see both safety and efficacy data at SITC and if you see anything that's a little more expensive at SITC versus what's in the abstract?
Leon Moulder
Thanks for the question, Seamus. Regarding VARUBI, and the IV in particular and Tim can chime in here in the moment. Obviously, the revenue recognition has to do with auditors call for us to the product actually moving all the way to patients and not having the opportunity for returns and expiring and all of that, that comes with a brand-new product launch when you're a midsize pharmaceutical company. But what we will do and I think this goes to your question is will provide color for the actual unit demand. We'll share what the unit demand is and then will you and the revenue gets recognized on that, to look at recognized. What you will understand the actual product uptake and the ramp of the launch based on unit demand. And related accounting take care of itself. Tim, anything to add?
Timothy Pearson
No that's right, Lonnie. From an oral standpoint, all of the oral is recognized when it leaves our warehouse and goes to the specialty pharmacies or specialty distributors. It's all recognized ex-factory out. With the IV, that will be recognized ex-factory but obviously given the state of the new launch in our history with the product the number of other factors there's likely to be some that wouldn't be recognized immediately.
Mary Hedley
So does that answer -- can we move on to the bevacizumab use and first line study of ovarian cancer. And we actually anticipated this, and that's why we started the OVARIO trial, which is our niraparib plus bevacizumab trial, which goes in the AVANOVA trial, which is in a current setting. So that's how we are seeing a tolerability of the combination and so meaningful data coming out of the AVANOVA trial with the medium PFS so far in a limited patient population of about 49 weeks. And Phase II portion of that is ongoing and will read out next year we'll complete the moment -- the enrollment will complete this year. But also not only in addition to OVARIO, we see the possibility and have considered, actually, the approval of that as we design the first study, which is over first-line study combination of niraparib plus 042. So in many ways, the real opportunity might be with triple combination in that setting. And then as it relates to TIM-3, the abstract that you have seen, which will be presented later this week is for the monotherapy.
So that 31 patients as you rightly pointed out in the dose escalation. And the data that you will be seeing will be safety as well as initial activity data. But again, this is a monotherapy setting and the patients who've been enrolled in the study are really those who don't really respond to PD-1 therapies. So there's typically the kind of patients who put on dose escalation phase. What's happened since then is that we've moved to a combination setting where we're testing 042 in combination with 022. And it that setting, we do see a lot more patients coming onto the trial who are actually either assistant to PD-1 therapy or naïve to PD-1 therapy. Who are more likely to have been lucky to stay PD-1. Does that help?
Operator
Our next question come from the line of Paul Choi of Barclays.
K. Choi
I had maybe a couple of commercial questions to start. Can you maybe update us on the mix of referral patients in the quarter versus new patients -- new patient adds?
Leon Moulder
Refills. Actually we're not prescribing that. One of the challenges there is we actually have a fairly large percentage for our business articles through specialty distributors, not through the specialty pharmacy. So we have, what that is for spur specialty pharmacy but for the specialty distributors, they ship the product to hospitals and to clinics that actually had been in office dispensing pharmacies. And we don't know the status of that unit how being used whether it's a new prescription or a refill. Now internally, we try to model to understand it. But I am -- that's got further along and the other thing is, I think all PARP inhibitor companies at some point here are probably going to unblock the data set so you'll be seeing all that on a regular basis.
K. Choi
Okay, great. And then on the European side, I think you noted to have about 350 patients or so on your expanded access program. Following the anticipated approval, when would those patients start to be recognized as commercial paid revenue patients in Europe?
Leon Moulder
Yes, and that's an excellent question. There's nuance to this as you know. In Germany, a launch happens almost immediately. And as I mentioned earlier, the largest portion of our EAP population are in Germany and the U.K. So the German EAP patients will move to commercial almost immediately. And then the -- that product utilized in Germany will be at a price that we establish. And then over a year, we negotiate what the long-term price will be. And then at the same time, we are obviously working on pricing and a multitude of other countries. In the first year, we'll make sales in Germany, portion of that will come from EAP patients who transfer to commercial. And then the other sales we'll get cash -- will be some of a bit of the same in the U.K. and then some of the Scandinavian countries.
As you get late into the year, you can think about perhaps France coming on board and then into the next year, Italy, Spain and others. But that's how this is all sequenced. And this is -- it's really a German launch at first. Everyone should remember that the number 1 pharmaceutical market in the world is in the U.S. Number 2 is Japan, number 3 Germany. It's a large market. Obviously China isn't certain categories. So we are excited to start selling in Germany here shortly. Pending approval, of course.
K. Choi
Great. And maybe one clinical question if I could. With regards to the plans Phase III of TSR-042 plus niraparib in lung, some of the other IO companies such [indiscernible] and Merck have both used or elevated overall survival as a primary endpoint. Is that a fair assumption for how TESARO is thinking about it, the clinical trial design? And then secondly, I think the Phase II, your combination trial that you're testing right now, I think you're using a mix of both Stage III and Stage IV patients, does Stage III maybe represent a better opportunity for you given that from the other companies in the stage IV metastatic market?
Mary Hedley
Sure. So our -- I guess I'll just say it, it's a little too early to tell you of the design of the studies in part that some of the work we are doing and monotherapy in combination study and trying to understand what's with the appropriate patient population from a biomarker perspective doing anything to slide the biomarker to pay patient population for that respond. So I guess what I can probably just say is that we have always tried to design clinical studies to be most relevant from a commercial perspective when we anticipate those studies actually reading out. And obviously, being approved so that on the market. So we will design this study in a way that should the data be positive, it will be a commercially viable opportunity for the -- for the combination.
Operator
Our next question comes from the line of Peter Lawson of SunTrust Robinson Humphrey.
Peter Lawson
The PD-1 combination along, what's the time for that data?
Mary Hedley
So we'll have some Phase II data towards, again, late middle next year. But that's preliminary data. And then obviously, the data matures, it will be a little bit longer. But it will be an update to help us decide effectively that Phase III study, which meant despite having first patients in Q4.
Peter Lawson
And then as we think about doctors prescribing ZEJULA, which of the easiest patients, which of the easiest doctors or convert? Is that the ones that are already using the narrower problems orders are the ones using vesting or those that are just not using anything and maintenance? How do kind of think about the easiest battlegrounds there?
Leon Moulder
That's a really good question. And I don't want to seem as if I'm not answering the question because it varies. If you did a nice job categorizing where there part for early adopters and can we get them on board. Are there people that just haven't used any of the PARP inhibitors and with our data set, we get them excited to do so in a broader population. And then there are patients -- people that have a lot of ovarian cancer. for use a lot of a bastion, they tend to use PARP or their little more resistant. But those are some of the key categories. And I would say it's a mix across all of them. Obviously, there is -- there's some people that have been working with niraparib forever so they're using a wrapper up so occasionally they will read sell side note on the survey and they asked the doctors and end up with the panel doctors have been using the wrapper up forever. I use 45% of the time niraparib.
Well clearly niraparib is only used 1/4 of the time of ZEJULA. So it's kind of a skewed panel. And then you see issues of questions of these niraparib abusers and it's all about the wrapper. But there niraparib abusers that obviously got her hands on the ZEJULA and moved to ZEJULA. So they may have been using niraparib initially in treatment but we prefer with the most compelling data and maintenance and now the moving to maintenance and are leaving treatment behind. And then they now have good experience with ZEJULA. Sosa makes. Now there are some advancing users that in a certain line, touring to sick with investment. And may be in front find they want to stick with niraparib and they're going to reserve our PARP inhibitor maintenance and the recurring setting because we are doing combination work with the best and so those data sets are available, anyone that's really stuck on Boston may move because the data says we can make a substantial difference for the patients. And that's what they may be waiting for. So surreal mix, Peter.
Operator
Our next question comes from the line of Steven Breazzano of Evercore ISI.
Steven Breazzano
Maybe just thinking about first line ovarian setting, would you expect longer treatment duration. Monotherapy and better hazard ratios as you move up from the second line setting and beyond? And in your experience, talking to physicians, is there a preference to use PARP inhibitors earlier?
Mary Hedley
So yes we would expect longer durations in the front line setting then we see in the recurring setting I believe by virtue of the fact that these patients are obviously so first line patients. So when we talk to physicians, they are actually really interested in moving PARP inhibitors out into the front line setting in particular for patients were stage III-for. I think we are likely going to see that in the Stage I/II patient. Because those patients just by definition if we have 85% of advanced patients having a recurrent stage I/II's are more likely to be the 15% that are cured from chemotherapy. So the risk benefit ratio might not be as appropriate for those patients as far as the PARP inhibiter goes. But when you have a 95% recurrence with advanced disease, I think there's a great desire to give those patients a better opportunity to avoid a recurrence or certainly delay a recurrence as long as possible because obviously once there is a recurrence, the patients likely to die of their disease. And we're even seeing that as long indicated. There is a small amount of use frontline sitting on ZEJULA even at this point in time.
Leon Moulder
And that's an important part of our strategy, of course. There will be old are all here discussing the PARP inhibitors and the recurrent maintenance acting, but really, the opportunity is to move this to the first line. And there, obviously, we have more patients, about 30% more patients but we also longer durations of therapy. And this makes it a bigger opportunity, obviously, from a marketing standpoint and value creation. So that's why we're taking it and that's why chromosome coordinates, the only PARP inhibitor therapy Phase III trial across a broad patient population regardless of biomarker status. And that's where we want to take this to next and quickly.
Operator
I'll now turn the call back over to Lonnie Moulder for any closing remarks.
Leon Moulder
Thank you, everyone, for joining us this evening. We really appreciate your interest, and we look forward to updating you along the way. Have a good evening.
Operator
Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program. You mail disconnect. Everyone, have a great day.
November 07, 2017, 16:15 ET
Executives
Jennifer Davis - VP of Corporate Communications & IR
Timothy Pearson - CFO and EVP
Leon Moulder - Co-Founder, CEO and Director
Mary Hedley - Co-Founder, President, COO and Director
Analysts
Tazeen Ahmad - Bank of America Merrill Lynch
Yanan Zhu - Wells Fargo Securities
Kennen MacKay - RBC Capital Markets
James Birchenough - Wells Fargo Securities
Charles Butler - Guggenheim Securities
Seamus Fernandez - Leerink Partners
K. Choi - Barclays PLC
Peter Lawson - SunTrust Robinson Humphrey
Steven Breazzano - Evercore ISI
Operator
Welcome to TESARO Third Quarter 2017 Conference Call. As a reminder, this call is being recorded and webcast. I'll now turn the call over to Jennifer Davis, Vice President of Investor Relations and Corporate Communications at TESARO. Please go ahead.
Jennifer Davis
Thank you, Nicole. Good afternoon, and thank you for joining us today to discuss our recent business progress and TESARO's third quarter 2017 operating results. With me here today are our CEO, Lonnie Mulder; our President and COO, Dr. Mary Hedley; and our CFO, Tim Pearson.
Earlier this afternoon, we issued a news release detailing our Q3 results. Please note that this news release and the slide presentation that we'll refer to during this conference call are both available in the Investors section of our website, www.tesarobio.com.
Before we begin, I'd like to remind you that discussions during this conference call will include forward-looking statements. These statements are subject to a number of risks and uncertainties that could cause our actual results to differ materially from those described in these forward-looking statements. We undertake no obligation to update or revise any forward-looking statements for any reason. The factors that could cause actual results to differ are discussed in the press release issued today and in our SEC filings, including our annual report on Form 10-K for the year ended December 31, 2016, and our quarterly report on Form 10-Q for the quarter ended June 30, 2017.
During today's call, we may refer to certain non-GAAP financial measures that involve certain non-GAAP figures. These non-GAAP financial measures are not a substitute for GAAP financial measures and are unlikely to be comparable to non-GAAP information provided by other companies. We believe non-GAAP measures may be useful to investors as a supplement to, but not as a substitute for, the applicable GAAP number. I'd now like to turn the call over to Lonnie Moulder, CEO of TESARO. Lonnie?
Leon Moulder
Thank you, Jen, thank you, everyone for joining us this afternoon. TESARO had an excellent quarter, marked by the successful launch of ZEJULA in the U.S, the positive CHMP opinion received for ZEJULA in Europe and progress on multiple fronts across our clinical development portfolio. Our first international launch, VARUBI oral is underway in Europe and we're well to prepared for 2 additional product launches before year-end, VARUBI IV in the U.S. and ZEJULA in Europe. The opportunities for ZEJULA to benefit patients extends well beyond ovarian cancer. And as Mary Lynn will describe today, we are prepared to initiate several Phase III trials in ovarian, lung and breast cancer to expand the ZEJULA franchise.
Our immune-oncology portfolio continues to rapidly advance and we now have 3 antibodies in the clinic targeting key immune checkpoints. We are rapidly advancing our registration trial of TSR-042, our anti-PD-1 antibody and our first IO/IO combination trial evaluating TSR-042, plus TSR-022, our anti-TIM-3 antibody is now enrolling patients.
I'd like to discuss the U.S. ZEJULA launch, which is off to a very strong start. The unsurpassed and compelling efficacy in ZEJULA as demonstrated in the NOVA Phase III study, combined with a, well-executed commercial strategy has produced a paradigm shift in the treatment of women with recurrent ovarian cancer, such that maintenance treatment with ZEJULA has quickly become a new standard of care. Following the introduction of ZEJULA, the number of women to resort to watchful waiting has declined remarkably. In addition to communicating the unsurpassed efficacy of ZEJULA in a broad patient population as demonstrated in the NOVA trial, our field force is effectively communicating a simple, elegant marketing message that resonates with clinicians. More time for more women.
During the third quarter, we experienced impressive growth in both the number of patients treated with ZEJULA as well as in the number of prescribing physicians. In September alone, approximately 2,500 patients were treated with ZEJULA and since approval, more than 1,700 unique healthcare providers had written a prescription for ZEJULA, including over 650 new prescribers in the third quarter. Utilization of ZEJULA has been evenly divided among patients with and without bracket BRCA mutations, and prescribers are about evenly split between community clinics and hospitals, both academic and community. Most new patients have started ZEJULA treatment at the 300 milligram dose and as expected, the average dose per prescription refills has moved towards 200 milligrams as physicians individualize the dose for their patients in a manner similar to what was observed in the NOVA trial. While still early in the launch, the duration of patient therapy is generally in line with our expectations. Noting that during the first weeks of product availability, some patients receiving ZEJULA -- received ZEJULA for later line treatment or began treatment after a prolonged platinum-free period while in response to platinum. Of course, durations of therapy in these patients would be shorter than for most patients who more closely represent the NOVA population.
Reimbursements coverage for ZEJULA is excellent, with more than 99% of life cover for ZEJULA across Medicare, Medicaid and private insurance. Approximately 60% of patients treated with ZEJULA had commercial insurance coverage and about 1/3 are covered by Medicare. Utilization of our patient assistance programs increased slightly from what was observed in the first quarter of launch and landed within the range of 25% to 30% of total unit volume, in line with other highly successful oral oncology products. The majority of patients assistance volume consists of patients who are unable to pay for the Medicare part [indiscernible] and who are impacted by the lack of nonprofit foundation assistance. In accordance with our mission, we've assigned our patient support programs to be appropriately comprehensive. We believe these programs are in the best interest of patients and support our belief that providers should choose ZEJULA as the preferred part inhibitor for recurrent ovarian cancer patients, who can benefit from maintenance treatment regardless of their ability to pay.
ZEJULA sales exceeded $39 million in the third quarter. And in September, ZEJULA captured approximately 60% of the U.S. part inhibitor market among patients with ovarian cancer, despite the recent label expansion of a competing product in the maintenance study. For comparison, in the first 6 weeks of availability, following launches, of the 2-part inhibitors indicated for maintenance treatment, approximately 4 times as many patients initiated treatment with ZEJULA as those who started maintenance treatment with the most recently approved part inhibitor in the comparable time period. Unsurpassed efficacy, convenient once daily dosing that easily adjusted to manage tolerability and a well-executed strategy has positioned ZEJULA to continue to be the market leader.
In Europe, strong uptake of our extended access or EIP -- EAP program continues. More than 350 patients have been treated to-date, with the largest participation occurring in Germany and the U.K, the number 1 and number 4 markets in Europe, respectively. Approximately 100 TESARO associates in Europe are actively engaged in prelaunch activities, and a European Commission approval of ZEJULA. This launch will begin in Germany, with subsequent launches in the U.K, Nordics and additional countries throughout 2018. The European comparative dynamic is highly favorable for ZEJULA. This single approved part inhibitor in Europe is indicated for maintenance treatment, which has provided a foundation for the maintenance paradigm in recurrent ovarian cancer, however, it is narrowly indicated for the minority of patients who harbor a BRCA mutation and is saddled with an unusually burdensome dosing regimen. By comparison, ZEJULA will launch as the only once daily part inhibitor for maintenance treatment, regardless of BRCA mutation status. We look forward to updating you on the launch next year.
2 weeks ago, the FDA approved VARUBI IV and we plan to launch this important product this month. VARUBI IV will provide clinicians with convenient, ready-to-use formulation in a ready-to-use infused bottle format without need for reconstitution or refrigeration. As a result, utilization and busy chemotherapy clinics is straightforward and easily adopted into existing practice patterns for administration of anti-medic regimens associated with chemotherapy. VARUBI IV is not only meaningful for patients, it is designed to address the needs of pharmacists and nurses who seek efficiencies and prefer not to spend staff time and resources reconstituting and mixing IV solutions, some of which are continually in short supply as required for the preparation and administration of the other IV and K-1 products. Importantly, with a total market opportunity consisting of 3 to 4 million doses per year, or nearly $1 billion annually, we believe VARUBI IV can be a substantial product for TESARO, serving as an efficient cash generator to support the development of our compelling and potentially transformational pipeline development programs. The IV formulation of VARUBI will enable us to reach the majority of the U.S. CIMB market and over time, extend the use of NK-1 receptor antagonists to the majority of patients receiving chemotherapy regimens including cisplatin, carboplatin and anthracycline cyclophosphamide combinations as recommended by the NCCN and ASCO guidelines. With that, I will now turn the call over to our CFO, Tim Pearson, for a review of our third quarter financial results. Tim?
Timothy Pearson
Thanks, Lenny. For the third quarter of 2017, TESARO reported total revenue of $142.8 million compared to $17 million for the third quarter of 2016. Net product revenue totaled $41.8 million for the third quarter of 2017 compared to $1.3 million for the third quarter of 2016. This growth was driven by the continued strong launch of ZEJULA in the U.S. ZEJULA net revenue totaled $39.4 million for the third quarter. Revenue from ZEJULA sales is recorded net of estimated discounts, returns, charge backs, rebates, co-pay assistance and other allowances. These gross to net adjustments represented approximately 10% of gross ZEJULA product sales for the third quarter. ZEJULA demand shipments from special distributors and specialty pharmacies increased sequentially by 87% for the third quarter compared to the second quarter this year. In the third quarter, approximately 65% of prescriptions were filled through our specialty pharmacy channel and the remainder were filled by specialty distributors.
VARUBI net revenue totaled $2.4 million for the third quarter compared to $1.3 million for the third quarter of 2016. As Lonnie said, we look forward to bringing our IV formulation of VARUBI to U.S. customers this month, which will enable us to reach the largest segment by far of the CINV market. License collaboration and other revenue totaled $101 million for the third quarter of 2017 compared to $15.7 million in Q3 2016. And included the $100 million upfront payment received as part of our Takeda license agreement.
Research and development expenses increased to $73.4 million for the third quarter compared to $60.8 million in Q3 of 2016. This increase was primarily driven by higher headcount, the advancement of our early-stage immune-oncology portfolio and expansion of the TSR-042 and TSR-022 programs. Selling, general and administrative expenses increased to $84 million for the third quarter compared to $37.7 million in Q3 of 2016. This is primarily due to increased headcount and other personnel related costs, activities in support of the launches of VARUBI and ZEJULA in the U.S. and Europe and higher professional service fees.
For Q3 2017, TESARO reported a net loss of $25.3 million compared to a net loss of $87.9 million for the third quarter of 2016. As of September 30, 2017, TESARO had approximately $521.3 million in cash and cash equivalents. This balance reflects operating cash utilization during the third quarter of approximately $94 million, excluding the $100 million upfront payment received as part of the Takeda license agreement. Looking ahead, we expect that our cash and cash equivalent balance will decrease by approximately $110 million to $120 million during the fourth quarter of 2017, excluding a $15 million milestone that we anticipate paying upon approval of ZEJULA in Europe.
With regard to ZEJULA, we expect net revenues of between $105 million and $115 million for the full year 2017. With the launch of the VARUBI IV, we expect to ship product at the end of this month and through December. The shipments will primarily be orders from providers taking advantage of launch discounts. Our ability to recognize those orders as revenue will depend on many factors and could be subject to constraint. At this time, we believe that only a portion of shipments will be recognized in the fourth quarter, but that will be determined at a later time. Our best estimate for IV revenue for the fourth quarter is in the range of mid-single digit millions of dollars. Additional guidance may be provided later in 2018 after we have established a demand pattern. With that, I'll hand the call over to Mary Lynn for an update on our development programs.
Mary Hedley
Thank you, Tim. Over the last year, the development pipeline has delivered 3 product approvals and we anticipate a fourth this month based on a positive CHMP opinion issued in September for the maintenance treatment of women with recurrent ovarian cancer following a response to platinum. With this approval in hand, we intend to launch ZEJULA in Europe before years end. So gratified by the success of our ongoing launch and the use of ZEJULA to meet the needs of women with recurrent ovarian cancer, we must and will do more. We intend for women across the full spectrum of ovarian cancer to benefit from ZEJULA, including those who are newly diagnosed. Patients with newly diagnosed ovarian cancer receive a standard regiment that includes surgery followed by six cycles of chemotherapy.
Subsequent to completion of chemotherapy, they are most often subjected to a watch and wait approach, but nearly 85% of those with advanced disease will experience a recurrence. We believe the treatment benefits of [indiscernible] immunotherapy can expand to this first-line maintenance study. And in so doing, provide even more time with for this large patient population, with limited or no other treatment options. We are effecting this possibility with the ongoing Phase III PRIMA study, where in the PFS benefit from niraparib treatment versus placebo control will be determined in patients with newly diagnosed stage III/IV ovarian cancer. Stratification factors for this study include the homologous recombination deficiency or HRD status of the tumor and the primary endpoint analysis will include a hierarchical step down for PFS, first in patients with HRD-positive tumors and just a result statistically significant than in the entire patient population.
And given a very robust enrollment rate in the study and our desire to gather clinical biomarker data that can be used to strengthen our competitive position in ovarian and other tumor types, we intend to expand this study from 330 to 468 patients. Despite the expansion, we continue to expect the enrollment will complete in the first part of next year and will be followed by data readout in 2019.
We are all aware that immunotherapy with anti-PD-1 antibodies has thus far offered unprecedented duration of clinical benefit across the large number of tumor studies. However, to date, women with ovarian cancer have proven relatively nonresponsive to this approach. We believe the addition of niraparib to our own anti-PD-1 antibody, TSR-042, could enable these women to experience the durable remissions provided by immunotherapy treatment. Our new Phase III frontline maintenance trial, first, has been agreed with major study groups and will initiate in the first half of next year, following completion of the ongoing clinical tolerability assessment of the TSR-042 and niraparib combination.
In Europe, newly diagnosed patients with ovarian cancer can receive the bevacizumab in combination with chemotherapy. And use bevacizumab in this study is now under review by FDA. Based upon the AVA NOVA data set, we believe a combination of bevacizumab and niraparib could provide compelling advancements for women in the front line setting. Next month, we expected dose a first patient in OVARIO, a Phase II study of niraparib in combination with bevacizumab in patients with newly diagnosed ovarian cancer. And we anticipate results from this study to be available in 2019.
For patients with recurrent ovarian cancer, we continue to explore the monotherapy benefit of ZEJULA in the ongoing QUADRA study and will supplement these efforts with our combination studies. Our success with the ZEJULA launch and interactions with practicing physicians has taught us the commercial value of avoiding, if possible, the use of complex tumor-based biomarker testing in the ovarian cancer Lateline treatment setting. Therefore, to optimize the differentiation and commercial opportunity of the QUADRA data set, prior to analyzing the response data, we are exploring the potential use of a blood-based biomarker to define a patient population which might best benefit from niraparib treatment. For this reason, data readout for QUADRA will likely be in Q1 of next year. Efforts to further lengthen niraparib treatment benefits for women with recurrent ovarian cancer will be via two approaches, a chemotherapy free bevacizumab combination and an IO combination with anti-PD-1 therapy. A chemotherapy free regimen for women who responded for at least 6 months to frontline platinum therapy has shown promise in the AVANOVA trial. AVANOVA conducted by our ENGOT collaborators is evaluating the combination of niraparib plus bevacizumab in patients with recurrent ovarian cancer. At ESMO, updated data was presented for part 1 of the study and demonstrated preliminary evidence of activity, with a median progression free survival of 49 weeks and an expected and manageable adverse event profile. We are encouraged by these early results and the potential for these 2 drugs in combination. The ongoing Phase II portion of this study in which patients are randomized to niraparib versus bevacizumab plus niraparib is ongoing and the trial is anticipated to complete enrollment this year, with data anticipated next year.
For those women with recurrent ovarian cancer whose last response to platinum was less than 6 months, we continue to advance TOPACIO, a clinical study of niraparib and an anti-PD-1 antibody. Patients with triple negative breast cancer are also being evaluated in this study. These tumors typically show relatively low response rates to anti-PD-1 antibody and PARP inhibitor monotherapy. And we hope to improve upon the clinical activity with this combination approach. Early data from TOPACIO was presented at ESMO in September. At the time of data presentation, 37% of platinum-resistant ovarian cancer patients and 44% of triple negative breast cancer patients remained on study treatment. And for patients with a PR or CR, most were continuing study treatment, further pointing to what is most important, durability of the response. We expect clarity around a potential registration study and additional data from this trial to become available in the first half of next year.
We see promise for niraparib that extends beyond ovarian cancer. Given the gene expansion deficiencies in patient with lung cancer, this tumor type is of particular interest as a potential opportunity for niraparib treatment. A large number of these patients have reduced expression of genes involved in DNA repair pathways, a higher rate of homologous recombination deficiency and platinum responsiveness. All hallmarks of sensitivity to PARP inhibition. Anti-PD-1 antibodies are approved for use in this setting. And based on TOPACIO and other data, may be effectively used in combination with the niraparib. Clinical studies are now ongoing, with the goal to assess the potential of niraparib and TSR-042 monotherapies as well as TSR-042 and niraparib combination therapy to provide benefit in this tumor setting. The studies will be used to define monotherapy disease control rate for each agent in patients with lung cancer, gather biomarker data and ultimately establish how vulnerability the preliminary activity of the niraparib plus TSR-042 combination, all to support our anticipated Phase III niraparib and TSR-042 lung study, which we will -- we expect will begin enrolling patients in the fourth quarter of 2018. More details on these studies will be provided at an appropriate time such that we can continue to maximize any competitive advantage in the space.
Our immuno-oncology programs remain on target with specific data results next year. Our current pipeline includes antibodies directed to PD-1, TIM-3 and LAG-3 and a bispecific to PD-1/LAG-3.
Beginning with TSR-042, our anti-PD-1 antibody. Patients with metastatic microsatellite instability high or MSI-high tumors, continue to enroll in the expansion phase of the ongoing GARNET study and receive a fixed dose of TSR-042 4 times, once every 3 weeks followed by administration every 6 weeks until disease progression. As previously discussed, we intend to use this study to support registration of TSR-042 in patients with MSI-high cancers and have agreed with FDA on this strategy. The primary efficacy in this trial are overall response rate and duration of response. At ESMO at September preliminary safety, efficacy, receptor occupancy and pharmacokinetic data for TSR-042 was presented, which indicated that TSR-042 has a safety and efficacy profile expected for an agent targeting the PD-1 pathway. We expect to share additional efficacy data from our expansion phase of this study in the second half of next year.
As you are aware, while anti-PD-1 therapy has proven effective in multiple tumor types, the response rates are typically low for any given unselected patient population. Many mechanisms are likely responsible for this observation, including an immunosuppressive tumor microenvironment brought about by the concerted actions of regulatory T cells, macrophages, [indiscernible] cells and the tumors themselves. The results, an effected T-cell population that is incapacitated and therefore, unable to sustain itself or it's ability to deal a definitive lethal blow to tumor cells. In the presence of a tumor-reactive effector T-cell population, continued support by the microenvironment is essential to retain maximum T-cell mediated killing. TIM-3 is expressed by multiple immune cells and intracellular signaling via TIM-3, dampens immune-mediated tumor cells on multiple fronts. TIM-3 ligand engagement causes the production of immunosuppressive molecules by regulatory T cells and then [indiscernible] cells and is a dominant negative signal in T-effector cells. Such that, even in the presence of anti-PD-1, these cells are not fully activated. Thus, blockade of TIM-3 expected to have multiple positive effects in the tumor microenvironment, including restoration of T-effector cell activity.
TSR-022 is our anti-TIM-3 antibody. Initial data from the dose escalation stage of our Phase I study of TSR-022 will be presented in the upcoming SITC meeting later this week. At the highest dose 10 mg [ph], several patients are still receiving treatment. And we anticipate that any clinical benefit derived from monotherapy treatment will be further enhanced by use of anti-TIM-3 in combination with TSR-042. A combination trial of TSR-022 plus TSR-042 at fixed doses of each antibody continues to enroll patients. The ongoing combination study will initially provide data to effect tolerability and identify the appropriate dose of TSR-022 to use in combination with TSR-042. And following this will be expanded to access activity in a cohort specific to patients with anti-PD-1 responsive tumors who are naïve to treatments and the cohort specific to patients with anti-PD-1 resistant tumor type. We look forward to showing initial data from this combination next year.
LAG-3 is also effect by effector T cells and is in part responsible for their inadequate antitumor response. While anti-LAG-3 has been shown to potentiate the effect of anti-PD-1 therapy in nonclinical and clinical studies, the most significant step forward may be recognized with the triple of combinations. Multiple nonclinical studies and different investigators including ourselves have demonstrated that a triplet is more effective than a doublet combinations of anti-PD-1 with anti-LAG-3 or anti-TIM-3 at causing tumor shrinkage regressions. And experiments using humanlike mice in a human tumor model, a combination of TSR-022, 042 and 033 was most effective at inhibiting tumor growth. In addition to the ongoing clinical studies with TSR-042 and TSR-022, TSR-033 our anti-LAG-3 antibody is well into a dose escalation Phase I clinical trial, utilizing a flat dose schedule. And combination studies with TSR-042 should initiate in a couple of months. The dose escalation phase of this study is enrolling all comers, and once the TSR-033 dose is identified to combine with TSR-042, cohorts will be instructed -- restricted to patient populations that are expected to benefit from the combination approach. The utilization of a flat dose and rapid expansion in the combination cohort will shorten the development timeline so that we are positioned to best optimize the combination approaches for our IO assets well into the future. And with that, I'll turn the call back over to Lonnie. Lonnie?
Leon Moulder
Thank you, Mary Lynn. Operator, this point, can we please open the call for questions?
Question-and-Answer Session
Operator
[Operator Instructions]. Our first question comes from the line of Robyn Karnauskas with Citigroup.
Unidentified Analyst
This is Krip [ph] on for Robyn. I just had a couple of questions about real world experience with ZEJULA. First question is about safety. Can you talk a little bit about how -- what sort of safety issues you've seen with patients, how doctors are managing, and any color on rates of discontinuation that you're seeing? And also can you talk a little bit about genetic test requirement. Are doctors requiring the genetic test even before residual or since it's been approved with a broad label, it seems like it's unnecessary?
Leon Moulder
Sure, and thanks for the question. I'll answer the first question first. There are no requirements related to genetic testing. The ZEJULA prescriptions are written for patients with recurrent ovarian cancer and 99% coverage across all areas including Medicare, Medicaid and commercial insurance. And obviously, that's what's allowed us to rapidly penetrate this market. So no genetic testing involved whatsoever. As far as the real world experience, it's actually quite similar to the NOVA study. So as you all know, if you look at the Phase III studies of PARP inhibitors in the recurrent ovarian cancer setting, all 3 agents had discontinuation rates in the 10% to 15% range. All 3 of them following the 10% to 15% range.
Some of the agents have a higher level of constitutional side effects. Things that patients feel. We believe we're better positioned than the other PARP inhibitors, with regards to those types of side effects. The one side effect that people point to that we've recognized relates to model suppression, again, something that all PARP inhibitors have. But ZEJULA actually has a higher incidence of thrombocytopenia. So grade 3, grade 4 thrombocytopenia was observed in the NOVA trial. And as you all know, what was reported is after cycle 2, the instance of grade 3, grade 4 of thrombocytopenia dropped to 1 or less percent. And the total amount of discontinuation in the NOVA trial related to thrombocytopenia was only 3%. So taking the experience from NOVA and understanding how thrombocytopenia should be managed, we established a communication and education program around our launch.
And what does that consist of? That ensures that physicians and nurses understand as patients receive their standard CBC blood test, to look at platelets and to expect, in the first cycle, approximately half of the patients will have a dose delay and move from the 30 -- 300 milligrams to the 200milligram, as per the NOVA study. And in the second cycle, additional patients will be dose adjusted. So what we do in the first 2 cycles, we ensure that clinicians know how to tailor the dose to that patients needs. We do that with our field force, with our oncology nurse educators who are informed whenever a prescription is written and with our specialty pharmacy partners who then call the patient on a weekly basis to establish a relationship and call the actual prescribing office. And in doing this, what we have found, as I described earlier, is that most of the prescriptions started 300 milligrams and the refills are now headed towards 200 milligrams.
So we would expect, as we said at the time of launch, that the average dose will be 200 milligrams, the most common dose will be 200 milligrams and that's really what we're seeing. From discontinuation rate, we're not seeing anything at all different than what was observed in the NOVA data. And as you can tell by the uptick on the drug, there are 4 times as many patients receiving ZEJULA and the benefits of ZEJULA, than patients who've been prescribing either of the other 2 PARP inhibitors. So I think the NOVA study taught us quite a bit and we have taken that message and that education to the clinicians. And although, ZEJULA's associated with a higher incidence of thrombocytopenia, the clinical sequelae are not at all unanticipated and no different than what was seen in the NOVA study. So we're keeping our patients safe. And we are ensuring that they are on a regiment that will lead to the benefits that we would expect them to receive, regardless of the dose they land on as observed in the NOVA study.
Unidentified Analyst
Great. That's very helpful. If I can just keep taking a follow-up question to the genetic test. Now since they're not doing a genetic test, is there anyway you guys can follow how the responses in HRD-negative patients is in the real world?
Mary Hedley
Not really, because they are not, again, doing the test.
Operator
Our next question comes from the line of Tazeen Ahmad of Bank of America.
Tazeen Ahmad
Maybe the first one on when we could potentially want to see some data from your non-small cell lung study that you are about to do. Whether it be interim or full data set? And then a question on TOPACIO. You told us in your press release that you were going to give us another update on the first of '18. Just wondering does that include longer follow ups for the patients that we were shown at ESMO? And if that would also include additional patients? And then I have one more follow-up?
Mary Hedley
Yes, so thank you for your question, Tazeen. The long trial data won't be available until probably in the middle of 2018. And again, that's preliminary data based on, first of all trying to understand the efficacy and safety in the immunotherapy study for each of the agents and then ultimately in combination. As it relates to TOPACIO, we anticipate yes, that you will see follow-up data from the patients that you saw at ESMO, in addition to several patients who didn't even have response rate data yet at ESMO.
Yanan Zhu
And is that likely an ASCO presentation?
Mary Hedley
That would be a reasonable expectation. I mean, I can't promise that, obviously.
Yanan Zhu
Right. Thanks. Then last question would be on the QUADRA study. When are you expecting results for that?
Mary Hedley
In Q1.
Operator
Our next question come from the line of Kennen McKay of RBC.
Kennen MacKay
Lonnie, maybe one for you. It seems like your marketing strategy for IV VARUBI changed historically from it being focused on contracting to one potentially taking advantage of some of the factors involved in the preparation of IV VARUBI versus IV amends. Can you maybe talk about the changes in the strategy there a little bit more?
Leon Moulder
Yes, so we are always enthusiastic about the design of the formulation because it is so easy. It's a little 100 milliliter bottle and it's already formulated. You just attach the IV line, there's actually a little hook already on the bottle so you then turn it upside down and put it on the IV pole and then infuse it in the patient in approximately 30 minutes within 2 hours of the chemotherapy. And we thought that was quite elegant, practical. As an old hospital pharmacist I just love it. But what's happen most recently is we've been -- we've had a large additional orders of oral VARUBI in centers that have been IV immense centers. And we investigated that and determined that what was being faced by many of these hospital pharmacies and clinic pharmacies was a shortage of sternal intravenous solutions for mixing drugs that come lyophilized or need to be diluted.
And the current IV participant is one of those drugs. You have to first dilute it in a vial, shake it after a while, then you have to get an IV bag and there's intermittent shortage of those, both Celine and dextrose, D5W and you in that bag then you have to refrigerate it until you get it to the patient. And watching all that happen and listening and doing some more qualitative market research, it became obvious that to us that there is a need that our elegant formulation matches really well. So it's sort of like a perfect storm that's taken place and we're leveraging that. So that's the fine-tuning of the strategy you are referring to Kennen.
Kennen MacKay
That's it. That's really helpful. And then just had a quick question on some of the guidance around the size of this market and one for Tim on potential guidance for ZEJULA. So just getting back to the size of the potential CINV market here. Regarding that sort of $1 billion potential, it seems like IV amends is sort of on a $550 million-ish run rate now. And so I was just wondering sort of what gets it up to that $1 billion market. The patient currently aren't being treated or again, sort of volume or maybe some additions on sort of the pricing growth or what should we be thinking about?
Leon Moulder
Excellent question, it's the former. It's really the percentage of patients who actually under both ASCO and NCCN guidelines, patients receiving platinum, carboplatinum cisplatin or women with breast cancer receiving AC recycle cyclophosphamide regimens, who were not receiving an NK-1. And we know from the Phase III studies of all of the NK-1 receptor antagonists, when you give the best care 5HT3 receptor antagonists in dexamethasone, 30% to 50% of those patients still go home, they vomit, they required rescue medication, they return to their clinics for hydration, they report to emergency rooms for hydration and for admissions. So that -- I mean, there's a reason why ASCO and NCCN says all those patients need to receive an NK-1. So it's now our job, with I think this opportunity with this formulation and our field force in our educational initiatives to actually maximize the opportunity for the whole class. So the class itself could be utilized 2 to 3 times more than it is today, under the guidelines. And that's why we size the opportunity being as large as $1 billion.
Kennen MacKay
That's it. Okay. And if I can just squeeze in one more maybe for Tim. I just wanted to make sure that 2017 guidance for ZEJULA right. I've heard of $105 million to $117 million. And if I did, it seems like on the lower end of that, that's not implying much quarter-over-quarter growth there. So just wanted to see if that was taking sort of an ultraconservative stance or is that was relating to anything new in the dynamics of [indiscernible] approval expansion?
Leon Moulder
Let me just comment on the reports was in turn it over to Tim. It's not at all related to the importance, we have via the IMS data. What they've done in the first 6 weeks of their launch, a few hundred patients, in addition to their normal baseline, which is 1/4 of what we obtained. And their growth actually, if you look at the intrinsic data, a substantial part of that relates to G BRCA breast cancer, not even on the ovarian study. So we're not seeing a lot of traction there on their behalf. And obviously, we had, if you recall, last time we talked about how we were going to do this year, we said something greater than 100, and now we have a range that I'll refer to Tim. Tim?
Timothy Pearson
Ronnie, the range that we quoted was $105 million to $115 million for the full year for ZEJULA.
Operator
And our next question comes from the line of Jim Birchenough of Wells Fargo Securities.
James Birchenough
So I guess on the 60% market share for ZEJULA, how sticky do you think that market share is? And maybe you could delve into what gives you the dominant market share and if you think you can maintain it? And related to that, whether contracting you think will be an important part of maintaining market share and whether over time you think you're going to get close to the discounted price maintaining that share, do you really think it's taking with the existing profile?
Timothy Pearson
Thanks for the question, Jim. As far as the market share, we talked about the market share on our second quarter. And from that point in time, which was June 30, to September, it's ticked up a couple of percentage points and that's in the face of [indiscernible]. So obviously, we're quite encouraged by that. The confirming we are getting good feedback from nurses, from support groups and obviously from physicians. And looking at any category of pharmaceuticals, the first to launch, the initial land grab as I say, is ours. So now that there are with an additional product and sometime next year a third product, how would those typically perform based on the fact that our data is unsurpassed. Our convenience is best and the value proposition we have relative to our 300, 200, 100 milligram dosing and pricing. How is it that they will take market share? Obviously, they'll get some share but the first to launch that's established itself this well, typically retains the largest market share.
So I would see stickiness. I'm not going to predict a specific market share that we're going to have long term. But I think there's enough analogs out there you can get a sense of the range of what that would be. So I guess that's how I would summarize where we are. Now going forward, of course, we have 175 people in the field across sales, account management, medical science liaisons, college nurse educators, providing solutions people. And share a voice and that is as strong as any large pharma or combination of live and work market and AstraZeneca would want to dedicate from their sales forces into ovarian cancer. So we're confident we are putting the right personnel resources in place. And then overall financial support of advertising and performance on medical education, our -- no, actually leaning towards the high end. So we think we'll be able to contingent -- continue to effectively compete, regardless of a change in the market dynamics based on the commitments we've made but importantly, how the product performs. And the data sets we've generated to date.
James Birchenough
And Lonnie, if I could just our follow-up for political of market expansion here. We have a sense of what proportion of patients that are eligible for second line maintenance receiving it right now? And are using any of the label uses for front line maintenance
Leon Moulder
Yes, so for all of the PARP inhibitors until this recent greater use in breast cancer for LYNPARZA, the ovarian use has been around 90%. The ovarian covers peroneal and fallopian tube. I guess -- I think, we're a little over 90% actually. Within ovarian, this is where it gets interesting [indiscernible] express out differently if you look at the different categories. First line maintenance, recurrent maintenance, early line treatment, late line treatment. The largest portion of our use, of course, is in recurrent maintenance. There is some late line treatment and there's also some first line maintenance with our drug. We have a mix. But the largest portion again is recurrent maintenance. And obviously, that is what we promote. That is what we educate on.
I'm just giving you a sense what's happening out there. So when you think about the market opportunity whether you look at the U.S. or Europe, there is about markets in Europe that we are targeting, they're about 10,000 patients that can benefit annually in each of the markets. So 20,000 in total. So about 10,000. If we just do the simple arithmetic on this, each week somewhere between 180 and 200 new patients become eligible because they're now in response to platinum, when you define the recurrent ovarian cancer markets. So if you look at our uptick today, you would say, we've had really nice penetration into that. We do get use elsewhere. But there's still another -- there's probably maybe 3 times as many patients, at least in the maintenance study that can be obtained as we continued on our launch trajectory. When you look at each pool of patients available on a weekly basis going forward. Does that make sense?
James Birchenough
That's really helpful. And maybe one final one from for Mary Lynn and that's just from TOPACIO, any reason why we won't see an update in San Antonio Breast Cancer symposium? And then on prospects for accelerated approval, do you have a sense of how many patients might be required and if that's a legitimate path?
Mary Hedley
So you won't see an update at San Antonio because the distance or duration of time between ESMO and San Antonio is really too short for us truly provide a meaningful update. So any updates that will happen will happen in the first half of next year and if that time will also define what the registration strategy will be for the combination approach. And we're thinking just based historically and with patients what we've seen from FDA, anywhere between 60 and 100 patients could be appropriate for an accelerated approval strategy.
Operator
Our next question comes from the line of Tony Butler of Guggenheim Security.
Charles Butler
Mary Lynn, just curious about the PD-1 strategy and the combinations. And I'm asking, if you combine 22 and/or 33 with 42 so PD-1 TIM-3 or LAG-3. And you're dosing at Q3 intervals and then move to Q6, the question is, what's the dose of the second combination agent? Does it also change? And then the second question is around they tell that has been presented before on T-cell exhaustion with one of the combination and I'm curious if, in fact, you might actually move forward in an IO refractory setting with the combo of a PD-1 plus 1 of the 2 other agents?
Mary Hedley
Sure, so that's a good question, Tony, the schedules. So we designed the scheduled 042 to be flexible to accommodate potential IO combinations or potential chemotherapy combinations given on a Q3 week or moving to Q6 week schedule. So as most of those other agents -- most of those chemotherapies are administered on a Q3 week basis, this would fit nicely with that. We would administer the chemotherapy at week 036 then you'd administer 042 at week 03 and then 6. And then as you progress further, you would just skip. Every chemo, every -- sorry, every third week you would be getting chemo, but every 6 week you would be getting chemo plus 042.
So it still fits nicely into the schedule. As we think about combining with 022 and 033, right now, we're thinking of maintaining a Q3 week schedule and we'll see during the combination will actually during the monotherapy and then the combinations, if we can move those agents to Q6 week as well. But right now, it's too early to predict that. And then related to your question on an IO refractory patient population, I'm going to assume by that question and correct me if I'm wrong, you mean tumor types that don't respond to PD-1 therapy, generally speaking. And yes, the intent is ultimately to also include those types of patients, because what we see from our tumor profiling experiments where we take fresh human tumors and look at tumor microenvironment, we see that even in a refractory -- even in tumor types that are refractory PD-1 therapy they do have T cells.
And in fact, there is a high level of TIM-3 and/or LAG-3 on those T cells in combination with PD-1. And we know that once those T cells express TIM-3 or LAG-3, a PD-1 antibody will not be sufficient to fully reactivate them so you really do need the combination therapy. So it is certainly one hypothesis as to why we don't see responses in certain tumor types such as, for example, call it to PD-1 therapy alone.
Charles Butler
And Mary Lynn, last question really on the same topic is, I'm really referring to -- also referring to IO refractory patients who can previously treated with an anti-PD-1 and for whatever reason it no longer has demonstrated regression of the tumor?
Mary Hedley
Yes, so we typically use the term resistant. So they have acquired resistance to PD-1 therapy meaning like a long our original melanoma patients that wasn't originally responding that is now progressed or has demonstrated progression on Petro Citi scanning following PD-1 therapy. So yes, we are actually including those patients. We will be turning them an expansion cohort and actually including them right now in our combination studies.
Operator
Our next question comes from the line of Ms. Seamus Fernandez of Leerink.
Seamus Fernandez
Maybe a couple of -- Lonnie, can you help us understand the context of VARUBI, when we can be confident that flow rates for both oral and IV VARUBI are likely to be booked as revenue and then we can sort of have a better understanding of where we are at a consistent run rate with regard to VARUBI? The second question is, as we think about the introduction of potential introduction of first-line and obviously the availability of second line of Astin plus chemo, can you just help us understand how you think that will actually affect the market for PARP maintenance? I think you can see 2 possibilities, you drag more patients into response and then actually expand the patient population. Or perhaps, alternatively, it could be viewed as not part of the regimens. I would just love to know how you're thinking about that. And the last question is, as we think about the opportunity for the other IO agents and your TIM-3 antibody, can you just give us a general sense of the number of patients? I think the abstract says 31 patients were treated. But in terms of the number of patients where we we'll see both safety and efficacy data at SITC and if you see anything that's a little more expensive at SITC versus what's in the abstract?
Leon Moulder
Thanks for the question, Seamus. Regarding VARUBI, and the IV in particular and Tim can chime in here in the moment. Obviously, the revenue recognition has to do with auditors call for us to the product actually moving all the way to patients and not having the opportunity for returns and expiring and all of that, that comes with a brand-new product launch when you're a midsize pharmaceutical company. But what we will do and I think this goes to your question is will provide color for the actual unit demand. We'll share what the unit demand is and then will you and the revenue gets recognized on that, to look at recognized. What you will understand the actual product uptake and the ramp of the launch based on unit demand. And related accounting take care of itself. Tim, anything to add?
Timothy Pearson
No that's right, Lonnie. From an oral standpoint, all of the oral is recognized when it leaves our warehouse and goes to the specialty pharmacies or specialty distributors. It's all recognized ex-factory out. With the IV, that will be recognized ex-factory but obviously given the state of the new launch in our history with the product the number of other factors there's likely to be some that wouldn't be recognized immediately.
Mary Hedley
So does that answer -- can we move on to the bevacizumab use and first line study of ovarian cancer. And we actually anticipated this, and that's why we started the OVARIO trial, which is our niraparib plus bevacizumab trial, which goes in the AVANOVA trial, which is in a current setting. So that's how we are seeing a tolerability of the combination and so meaningful data coming out of the AVANOVA trial with the medium PFS so far in a limited patient population of about 49 weeks. And Phase II portion of that is ongoing and will read out next year we'll complete the moment -- the enrollment will complete this year. But also not only in addition to OVARIO, we see the possibility and have considered, actually, the approval of that as we design the first study, which is over first-line study combination of niraparib plus 042. So in many ways, the real opportunity might be with triple combination in that setting. And then as it relates to TIM-3, the abstract that you have seen, which will be presented later this week is for the monotherapy.
So that 31 patients as you rightly pointed out in the dose escalation. And the data that you will be seeing will be safety as well as initial activity data. But again, this is a monotherapy setting and the patients who've been enrolled in the study are really those who don't really respond to PD-1 therapies. So there's typically the kind of patients who put on dose escalation phase. What's happened since then is that we've moved to a combination setting where we're testing 042 in combination with 022. And it that setting, we do see a lot more patients coming onto the trial who are actually either assistant to PD-1 therapy or naïve to PD-1 therapy. Who are more likely to have been lucky to stay PD-1. Does that help?
Operator
Our next question come from the line of Paul Choi of Barclays.
K. Choi
I had maybe a couple of commercial questions to start. Can you maybe update us on the mix of referral patients in the quarter versus new patients -- new patient adds?
Leon Moulder
Refills. Actually we're not prescribing that. One of the challenges there is we actually have a fairly large percentage for our business articles through specialty distributors, not through the specialty pharmacy. So we have, what that is for spur specialty pharmacy but for the specialty distributors, they ship the product to hospitals and to clinics that actually had been in office dispensing pharmacies. And we don't know the status of that unit how being used whether it's a new prescription or a refill. Now internally, we try to model to understand it. But I am -- that's got further along and the other thing is, I think all PARP inhibitor companies at some point here are probably going to unblock the data set so you'll be seeing all that on a regular basis.
K. Choi
Okay, great. And then on the European side, I think you noted to have about 350 patients or so on your expanded access program. Following the anticipated approval, when would those patients start to be recognized as commercial paid revenue patients in Europe?
Leon Moulder
Yes, and that's an excellent question. There's nuance to this as you know. In Germany, a launch happens almost immediately. And as I mentioned earlier, the largest portion of our EAP population are in Germany and the U.K. So the German EAP patients will move to commercial almost immediately. And then the -- that product utilized in Germany will be at a price that we establish. And then over a year, we negotiate what the long-term price will be. And then at the same time, we are obviously working on pricing and a multitude of other countries. In the first year, we'll make sales in Germany, portion of that will come from EAP patients who transfer to commercial. And then the other sales we'll get cash -- will be some of a bit of the same in the U.K. and then some of the Scandinavian countries.
As you get late into the year, you can think about perhaps France coming on board and then into the next year, Italy, Spain and others. But that's how this is all sequenced. And this is -- it's really a German launch at first. Everyone should remember that the number 1 pharmaceutical market in the world is in the U.S. Number 2 is Japan, number 3 Germany. It's a large market. Obviously China isn't certain categories. So we are excited to start selling in Germany here shortly. Pending approval, of course.
K. Choi
Great. And maybe one clinical question if I could. With regards to the plans Phase III of TSR-042 plus niraparib in lung, some of the other IO companies such [indiscernible] and Merck have both used or elevated overall survival as a primary endpoint. Is that a fair assumption for how TESARO is thinking about it, the clinical trial design? And then secondly, I think the Phase II, your combination trial that you're testing right now, I think you're using a mix of both Stage III and Stage IV patients, does Stage III maybe represent a better opportunity for you given that from the other companies in the stage IV metastatic market?
Mary Hedley
Sure. So our -- I guess I'll just say it, it's a little too early to tell you of the design of the studies in part that some of the work we are doing and monotherapy in combination study and trying to understand what's with the appropriate patient population from a biomarker perspective doing anything to slide the biomarker to pay patient population for that respond. So I guess what I can probably just say is that we have always tried to design clinical studies to be most relevant from a commercial perspective when we anticipate those studies actually reading out. And obviously, being approved so that on the market. So we will design this study in a way that should the data be positive, it will be a commercially viable opportunity for the -- for the combination.
Operator
Our next question comes from the line of Peter Lawson of SunTrust Robinson Humphrey.
Peter Lawson
The PD-1 combination along, what's the time for that data?
Mary Hedley
So we'll have some Phase II data towards, again, late middle next year. But that's preliminary data. And then obviously, the data matures, it will be a little bit longer. But it will be an update to help us decide effectively that Phase III study, which meant despite having first patients in Q4.
Peter Lawson
And then as we think about doctors prescribing ZEJULA, which of the easiest patients, which of the easiest doctors or convert? Is that the ones that are already using the narrower problems orders are the ones using vesting or those that are just not using anything and maintenance? How do kind of think about the easiest battlegrounds there?
Leon Moulder
That's a really good question. And I don't want to seem as if I'm not answering the question because it varies. If you did a nice job categorizing where there part for early adopters and can we get them on board. Are there people that just haven't used any of the PARP inhibitors and with our data set, we get them excited to do so in a broader population. And then there are patients -- people that have a lot of ovarian cancer. for use a lot of a bastion, they tend to use PARP or their little more resistant. But those are some of the key categories. And I would say it's a mix across all of them. Obviously, there is -- there's some people that have been working with niraparib forever so they're using a wrapper up so occasionally they will read sell side note on the survey and they asked the doctors and end up with the panel doctors have been using the wrapper up forever. I use 45% of the time niraparib.
Well clearly niraparib is only used 1/4 of the time of ZEJULA. So it's kind of a skewed panel. And then you see issues of questions of these niraparib abusers and it's all about the wrapper. But there niraparib abusers that obviously got her hands on the ZEJULA and moved to ZEJULA. So they may have been using niraparib initially in treatment but we prefer with the most compelling data and maintenance and now the moving to maintenance and are leaving treatment behind. And then they now have good experience with ZEJULA. Sosa makes. Now there are some advancing users that in a certain line, touring to sick with investment. And may be in front find they want to stick with niraparib and they're going to reserve our PARP inhibitor maintenance and the recurring setting because we are doing combination work with the best and so those data sets are available, anyone that's really stuck on Boston may move because the data says we can make a substantial difference for the patients. And that's what they may be waiting for. So surreal mix, Peter.
Operator
Our next question comes from the line of Steven Breazzano of Evercore ISI.
Steven Breazzano
Maybe just thinking about first line ovarian setting, would you expect longer treatment duration. Monotherapy and better hazard ratios as you move up from the second line setting and beyond? And in your experience, talking to physicians, is there a preference to use PARP inhibitors earlier?
Mary Hedley
So yes we would expect longer durations in the front line setting then we see in the recurring setting I believe by virtue of the fact that these patients are obviously so first line patients. So when we talk to physicians, they are actually really interested in moving PARP inhibitors out into the front line setting in particular for patients were stage III-for. I think we are likely going to see that in the Stage I/II patient. Because those patients just by definition if we have 85% of advanced patients having a recurrent stage I/II's are more likely to be the 15% that are cured from chemotherapy. So the risk benefit ratio might not be as appropriate for those patients as far as the PARP inhibiter goes. But when you have a 95% recurrence with advanced disease, I think there's a great desire to give those patients a better opportunity to avoid a recurrence or certainly delay a recurrence as long as possible because obviously once there is a recurrence, the patients likely to die of their disease. And we're even seeing that as long indicated. There is a small amount of use frontline sitting on ZEJULA even at this point in time.
Leon Moulder
And that's an important part of our strategy, of course. There will be old are all here discussing the PARP inhibitors and the recurrent maintenance acting, but really, the opportunity is to move this to the first line. And there, obviously, we have more patients, about 30% more patients but we also longer durations of therapy. And this makes it a bigger opportunity, obviously, from a marketing standpoint and value creation. So that's why we're taking it and that's why chromosome coordinates, the only PARP inhibitor therapy Phase III trial across a broad patient population regardless of biomarker status. And that's where we want to take this to next and quickly.
Operator
I'll now turn the call back over to Lonnie Moulder for any closing remarks.
Leon Moulder
Thank you, everyone, for joining us this evening. We really appreciate your interest, and we look forward to updating you along the way. Have a good evening.
Operator
Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program. You mail disconnect. Everyone, have a great day.