Post by icemandios on Nov 8, 2022 19:53:46 GMT
November 8, 2022 12:01 PM ESTUpdated 01:18 PM R&D
Starting with ADC, FDA calls for fully enrolled confirmatory trial prior to accelerated approval submission
Zachary Brennan
Senior Editor
When Congress punted on adding new accelerated approval reforms to the user fee legislation, many wondered how and when the agency would get around to fixing the issue of ensuring these confirmatory trials are completed in a more timely manner.
Now, FDA appears to be taking the matter into its own hands.
ADC Therapeutics said on Tuesday, as part of its Q3 earnings report, that it’s taking a step back to reevaluate its experimental CD25-targeted ADC Cami (camidanlumab tesirine) after the FDA “provided strong guidance that, for it to consider an accelerated approval path, a randomized confirmatory Phase 3 study must be well underway and ideally fully enrolled at the time of any BLA filing.”
The guidance from FDA, if what ADC is saying is true and it’s applied to others seeking accelerated approvals, could, on the one hand, move the needle in terms of accelerating the enrolment of confirmatory trials, many of which can go on for years. But on the other hand, it could push smaller companies away from this pathway as some may not have the capital to set up a confirmatory trial before reaping the benefits of an accelerated approval.
Regeneron CEO Len Schleifer also echoed what ADC is saying, noting in his most recent earnings call that “the regulators have recently been focused on having phase three trials, substantially enrolled at the time of submission, before they’ll grant accelerated approval.”
Officials from FDA’s Oncology Center of Excellence previously made clear the need to ensure confirmatory trials are underway when an accelerated approval is granted, as they showed a median time to withdrawal of 3.8 years if the confirmatory trial was ongoing at the time of approval, compared with 7.3 years if such a trial had not been initiated.
FDA's OCE makes the case for accelerated approval rider in user fee reauthorization
But as a result of this guidance, the Switzerland-based company said it likely wouldn’t file its BLA for Cami next year, as the company says it’ll take at least two years to fully enroll an RCT. And while the company says it’s engaged with FDA on moving Cami forward, it’s also “pausing any material investments” into the Hodgkin’s lymphoma program and will evaluate its options.
Last June, ADC reported that in a Phase II trial of 117 patients with r/r Hodgkin’s lymphoma who received ≥3 prior lines of treatment, Cami’s overall response rate was 70% and complete response rate was 33%, with a median duration of response of 13.7 months.
Meanwhile, ADC halted another Phase 1b study of Cami in combination with Keytruda in solid tumors, adding that it “recognizes the considerable effort required to fully pursue this opportunity may be better suited for a partner with immuno-oncology development expertise.”
The blows to Cami follow ADC’s decision last year to enter into a royalty deal where the company would receive $225 million in cash and an additional $100 million in near-term milestones as part of a royalty sale with HealthCare Royalty for its lead antibody-drug conjugate Zynlonta and investigational CD25 candidate camidanlumab tesirine (Cami), the companies said Thursday.
But the shift for FDA shows the agency may have more wiggle room than previously thought when it comes to what to require prior to a BLA filing.
“I do think that, in general, the agency could exert greater power to control the terms of the [accelerated approval] program than it has previously,” Rachel Sachs, law professor at Washington University School of Law in St. Louis. “This is one pretty clear example. I understand why the agency would prefer to have clearer statutory authority to do this, but there’s an argument that the terms of the program permit it already.”
Starting with ADC, FDA calls for fully enrolled confirmatory trial prior to accelerated approval submission
Zachary Brennan
Senior Editor
When Congress punted on adding new accelerated approval reforms to the user fee legislation, many wondered how and when the agency would get around to fixing the issue of ensuring these confirmatory trials are completed in a more timely manner.
Now, FDA appears to be taking the matter into its own hands.
ADC Therapeutics said on Tuesday, as part of its Q3 earnings report, that it’s taking a step back to reevaluate its experimental CD25-targeted ADC Cami (camidanlumab tesirine) after the FDA “provided strong guidance that, for it to consider an accelerated approval path, a randomized confirmatory Phase 3 study must be well underway and ideally fully enrolled at the time of any BLA filing.”
The guidance from FDA, if what ADC is saying is true and it’s applied to others seeking accelerated approvals, could, on the one hand, move the needle in terms of accelerating the enrolment of confirmatory trials, many of which can go on for years. But on the other hand, it could push smaller companies away from this pathway as some may not have the capital to set up a confirmatory trial before reaping the benefits of an accelerated approval.
Regeneron CEO Len Schleifer also echoed what ADC is saying, noting in his most recent earnings call that “the regulators have recently been focused on having phase three trials, substantially enrolled at the time of submission, before they’ll grant accelerated approval.”
Officials from FDA’s Oncology Center of Excellence previously made clear the need to ensure confirmatory trials are underway when an accelerated approval is granted, as they showed a median time to withdrawal of 3.8 years if the confirmatory trial was ongoing at the time of approval, compared with 7.3 years if such a trial had not been initiated.
FDA's OCE makes the case for accelerated approval rider in user fee reauthorization
But as a result of this guidance, the Switzerland-based company said it likely wouldn’t file its BLA for Cami next year, as the company says it’ll take at least two years to fully enroll an RCT. And while the company says it’s engaged with FDA on moving Cami forward, it’s also “pausing any material investments” into the Hodgkin’s lymphoma program and will evaluate its options.
Last June, ADC reported that in a Phase II trial of 117 patients with r/r Hodgkin’s lymphoma who received ≥3 prior lines of treatment, Cami’s overall response rate was 70% and complete response rate was 33%, with a median duration of response of 13.7 months.
Meanwhile, ADC halted another Phase 1b study of Cami in combination with Keytruda in solid tumors, adding that it “recognizes the considerable effort required to fully pursue this opportunity may be better suited for a partner with immuno-oncology development expertise.”
The blows to Cami follow ADC’s decision last year to enter into a royalty deal where the company would receive $225 million in cash and an additional $100 million in near-term milestones as part of a royalty sale with HealthCare Royalty for its lead antibody-drug conjugate Zynlonta and investigational CD25 candidate camidanlumab tesirine (Cami), the companies said Thursday.
But the shift for FDA shows the agency may have more wiggle room than previously thought when it comes to what to require prior to a BLA filing.
“I do think that, in general, the agency could exert greater power to control the terms of the [accelerated approval] program than it has previously,” Rachel Sachs, law professor at Washington University School of Law in St. Louis. “This is one pretty clear example. I understand why the agency would prefer to have clearer statutory authority to do this, but there’s an argument that the terms of the program permit it already.”