Post by tomsylver on Apr 10, 2017 12:27:44 GMT
Apr. 6, 2017
Summary
I was at the Society for Gynecologic Oncology in National Harbor, wondering if the blizzard was going to subside long enough to get on a plane back home (it did), when Tesaro's (NASDAQ:TSRO) and AstraZeneca's PARP inhibition data came down the pipe. This time, it was TSRO's turn to suffer some losses after SOLO2 demonstrated strongly favorable results in women with BRCA-mutant ovarian cancer.
As TSRO fell $20 from the opening bell, I thought "investors are crazy." This company is about to see approval for niraparib without the need for a biomarker test, since results of NOVA showed that it could provide significant benefit across a wider range of patients than previously expected.
Then, niraparib was approved not two weeks later, and I poised myself to think about how right I was and how this would vindicate my optimism in TSRO immediately. How wrong I was! It just goes to show you that you can never predict the market, no matter how sure things seem.
Of course, it makes sense. Niraparib looked poised to get the first and only approval for recurrent ovarian cancer in the "maintenance" setting, but SOLO-2 and the subsequent priority review for olaparib in this setting means there's significant competition ahead in the US.
TSRO Moving Forward
But this post-approval pessimism is likely to be short-lived, in my opinion. TSRO announced that it is advancing the niraparib project far, and quickly. They have spidered out into three areas of interest:
1. Frontline metastatic ovarian cancer
2. Metastatic breast cancer
3. Lung cancer
The first of these indications is no shock. Upon success for recurrent disease, it's natural to move toward testing PARP inhibition in the front line. Of course, it has competition. Lynparza is being assessed in the maintenance setting post-first-line chemotherapy, the so-called SOLO-1 study. This study continues to limit patients to those who are BRCA-positive, which represents up to 40% of patients, depending on how you measure.
The first-line PRIMA study and the heavily pretreated QUADRA study have been optimized to account for the benefit seen in NOVA. This could yet provide another edge for niraparib as the use of PARP inhibition in ovarian cancer continues to evolve. Other studies, like OvCa 3000-03-003 and TOPACIO, are combining niraparib with PD-1 antibodies like Keytruda.
Movement in breast cancer
Because of the well-known prevalence of BRCA mutations in breast cancer, PARP inhibition has seemed like a natural fit for study in this space, since blocking PARP cuts off the tumor's ability to repair any DNA, forcing it into cell death. Unfortunately, it has taken a while to define the potential role of these agents in breast cancer. Recently, press released results from the OLYMPIAD trial showed that Lynparza could improve progression-free survival in HER2-negative, BRCA-positive metastatic breast cancer compared with chemotherapy.
For niraparib, the picture is a little less clear. In metastatic disease, the BRAVO study doesn't look like it will shape up well. A larger-than-expected number of women in the control chemotherapy arm dropped out before the first radiologic scan, forcing their results to be censored. Though this may be because these women would rather receive PARP inhibitors for their BRCA-positive breast cancer, it makes the study very difficult to interpret.
Now, BRAVO results will be used to inform a planned study involving niraparib combined with an immune checkpoint inhibitor for triple-negative breast cancer, which remains a substantial unmet need.
Movement in lung cancer
Perhaps PARP inhibition as a treatment strategy for lung cancer seems a bit off-the-wall. These tumors are not associated with BRCA mutation to a significant extent. However, other forms of DNA repair deficiency may yet provide a rationale for adding PARP inhibitors to treatment.
As such, TSRO is moving forward with PARP inhibitor studies in lung. These include studies comparing niraparib monotherapy with niraparib plus an anti-PD-1 antibody (Lung 3000-02-001) in advanced squamous cell lung cancer, which is a notoriously challenging subtype to treat.
Lung 3000-03-001 is a phase 3 trial comparing the niraparib/anti-PD-1 combination to anti-PD-1 alone in patients with advanced NSCLC and high PD-L1 expression. The press release was not specific, but I presume that histology doesn't matter (includes both squamous and non-squamous disease), and that it may be an investigation in the first line. Though this is unclear.
Conclusions and risks
TSRO has passed a big hurdle for niraparib, the first approval. Rapid expansion into other indications is now needed to expand the franchise, and it is a very good sign that TSRO is providing excellent guidance on how it intends to move niraparib forward. It appears to me like TSRO could quickly differentiate itself from AZD when it comes to these PARP inhibitors, and it is not clear at this time which patients should receive which inhibitor, niraparib or Lynparza.
As more clinicians become familiar with PARP inhibitors, you're going to see the sales of these agents climb quickly, I imagine. It's difficult to tell right now, but I think this is recent downturn is going to be a temporary slump for TSRO's valuation.
But to be fair, it is also worth considering the risks involved in a TSRO position. AZD is a major competitor with substantial backing for Lynparza, and their recent SOLO-2 results demonstrate that they are basically keeping pace. TSRO may be able to capture a chunk of the market by being first for non-germline-BRCA patients, but AZD has demonstrated its willingness to keep pace. Also, it is always unpredictable how these clinical trials will go, so investing based on the initiation and expansion of studies represents a major risk.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
seekingalpha.com/article/4060896-tesaro-steamrolling-parp-inhibitors
Summary
- Tesaro has nailed approval for its remarkable PARP inhibitor, niraparib.
- Competition in the ovarian cancer space is about to spill out onto other tumor types.
- Tesaro is expanding its programs quickly.
I was at the Society for Gynecologic Oncology in National Harbor, wondering if the blizzard was going to subside long enough to get on a plane back home (it did), when Tesaro's (NASDAQ:TSRO) and AstraZeneca's PARP inhibition data came down the pipe. This time, it was TSRO's turn to suffer some losses after SOLO2 demonstrated strongly favorable results in women with BRCA-mutant ovarian cancer.
As TSRO fell $20 from the opening bell, I thought "investors are crazy." This company is about to see approval for niraparib without the need for a biomarker test, since results of NOVA showed that it could provide significant benefit across a wider range of patients than previously expected.
Then, niraparib was approved not two weeks later, and I poised myself to think about how right I was and how this would vindicate my optimism in TSRO immediately. How wrong I was! It just goes to show you that you can never predict the market, no matter how sure things seem.
Of course, it makes sense. Niraparib looked poised to get the first and only approval for recurrent ovarian cancer in the "maintenance" setting, but SOLO-2 and the subsequent priority review for olaparib in this setting means there's significant competition ahead in the US.
TSRO Moving Forward
But this post-approval pessimism is likely to be short-lived, in my opinion. TSRO announced that it is advancing the niraparib project far, and quickly. They have spidered out into three areas of interest:
1. Frontline metastatic ovarian cancer
2. Metastatic breast cancer
3. Lung cancer
The first of these indications is no shock. Upon success for recurrent disease, it's natural to move toward testing PARP inhibition in the front line. Of course, it has competition. Lynparza is being assessed in the maintenance setting post-first-line chemotherapy, the so-called SOLO-1 study. This study continues to limit patients to those who are BRCA-positive, which represents up to 40% of patients, depending on how you measure.
The first-line PRIMA study and the heavily pretreated QUADRA study have been optimized to account for the benefit seen in NOVA. This could yet provide another edge for niraparib as the use of PARP inhibition in ovarian cancer continues to evolve. Other studies, like OvCa 3000-03-003 and TOPACIO, are combining niraparib with PD-1 antibodies like Keytruda.
Movement in breast cancer
Because of the well-known prevalence of BRCA mutations in breast cancer, PARP inhibition has seemed like a natural fit for study in this space, since blocking PARP cuts off the tumor's ability to repair any DNA, forcing it into cell death. Unfortunately, it has taken a while to define the potential role of these agents in breast cancer. Recently, press released results from the OLYMPIAD trial showed that Lynparza could improve progression-free survival in HER2-negative, BRCA-positive metastatic breast cancer compared with chemotherapy.
For niraparib, the picture is a little less clear. In metastatic disease, the BRAVO study doesn't look like it will shape up well. A larger-than-expected number of women in the control chemotherapy arm dropped out before the first radiologic scan, forcing their results to be censored. Though this may be because these women would rather receive PARP inhibitors for their BRCA-positive breast cancer, it makes the study very difficult to interpret.
Now, BRAVO results will be used to inform a planned study involving niraparib combined with an immune checkpoint inhibitor for triple-negative breast cancer, which remains a substantial unmet need.
Movement in lung cancer
Perhaps PARP inhibition as a treatment strategy for lung cancer seems a bit off-the-wall. These tumors are not associated with BRCA mutation to a significant extent. However, other forms of DNA repair deficiency may yet provide a rationale for adding PARP inhibitors to treatment.
As such, TSRO is moving forward with PARP inhibitor studies in lung. These include studies comparing niraparib monotherapy with niraparib plus an anti-PD-1 antibody (Lung 3000-02-001) in advanced squamous cell lung cancer, which is a notoriously challenging subtype to treat.
Lung 3000-03-001 is a phase 3 trial comparing the niraparib/anti-PD-1 combination to anti-PD-1 alone in patients with advanced NSCLC and high PD-L1 expression. The press release was not specific, but I presume that histology doesn't matter (includes both squamous and non-squamous disease), and that it may be an investigation in the first line. Though this is unclear.
Conclusions and risks
TSRO has passed a big hurdle for niraparib, the first approval. Rapid expansion into other indications is now needed to expand the franchise, and it is a very good sign that TSRO is providing excellent guidance on how it intends to move niraparib forward. It appears to me like TSRO could quickly differentiate itself from AZD when it comes to these PARP inhibitors, and it is not clear at this time which patients should receive which inhibitor, niraparib or Lynparza.
As more clinicians become familiar with PARP inhibitors, you're going to see the sales of these agents climb quickly, I imagine. It's difficult to tell right now, but I think this is recent downturn is going to be a temporary slump for TSRO's valuation.
But to be fair, it is also worth considering the risks involved in a TSRO position. AZD is a major competitor with substantial backing for Lynparza, and their recent SOLO-2 results demonstrate that they are basically keeping pace. TSRO may be able to capture a chunk of the market by being first for non-germline-BRCA patients, but AZD has demonstrated its willingness to keep pace. Also, it is always unpredictable how these clinical trials will go, so investing based on the initiation and expansion of studies represents a major risk.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
seekingalpha.com/article/4060896-tesaro-steamrolling-parp-inhibitors