Sarepta Therapeutics will not publicly criticize the Food and Drug Administration for rejecting its Duchenne muscular dystrophy drug Vyondys 53, nor ask patient advocacy groups to pressure the agency to change its mind.
This message from CEO Doug Ingram, delivered during a third quarter earnings call yesterday, shows how much the biotech has changed from when it last tried to get a drug approved.
The tense relationship between Sarepta and FDA reviewers over the relevance of biomarker and functional data was one of the reasons the agency nearly turned back Exondys 51. Only after very unusual intervention from senior FDA officials — and vocal encouragement from patient advocates encouraged by the company — did the drug win approval.
Ingram, however, says he wants no part of that — a departure from his predecessors Edward Kaye and Chris Garabedian, who each previously served as CEOs of Sarepta.
"I've heard from those who would prefer that I speak more often more publicly on this issue, and/or that I would attempt to engage the patient community or others to assist, for instance, in applying external pressure to bring this therapy a lot faster," he said during the earnings call. "I have no intention of doing either of those things."
"If we can win the day with this therapy and with this issue, we will have done so on the science, and on the regulations and in collaborative evidence-based discussions with our reviewers at the FDA," Ingram added.
He also attempted to end speculation the Complete Response Letter that Sarepta received for Vyondys 53 was driven by agency politics related to the company's failure to advance a confirmatory trial for Exondys 51.
"I remain convinced that we were treated very fairly and professionally by the division of neurology," Ingam said. "From my perspective, we have gone a long way in the last two and a half years in forging a positive evidence-based working relationship with the division."
FDA documents released after Exondys 51's approval showed how adversarial the review had been, with agency staff charging that the company exaggerated the benefits shown in its clinical studies and inappropriately raised expectations in the patient community the FDA would not require additional trials before approval.
Agency officials at the Division of Neurology Products, as well as the then-director of the Office of New Drugs and the acting chief scientist, supported issuing a Complete Response Letter for Exondys 51, citing a lack of sufficient evidence proving the drug's benefit.
Intervention by Janet Woodcock, head of the FDA's Center for Drug Evaluation and Research, was required to push Exondys 51 over the line.
The Vyondys 53 rejection, which was based on data regarding infection and kidney toxicity risks, cast doubt on whether Sarepta will submit a follow-up drug called casimersen for review. That drug uses the same platform as Vyondys 53.
Speaking on the call Thursday, Ingram confirmed Sarepta will hold casimersen's FDA application until the Complete Response Letter for Vyondys 53 is resolved.
Analysts from SVB Leerink and RBC Capital Markets raised the possibility that, as the FDA is restructuring, key personnel in the Office of Drug Evaluation I could be moved off of the Vyondys 53 review. The head of that office, Ellis Unger, was among the FDA personnel who objected to Exondys 51.
Nonetheless, Leerink's Joseph Schwartz said the signals being sent by Ingram have prompted him to lower the chance of Vyondys' success from 75% to 50%.
Schwartz was joined by Cantor Fitzgerald's Alethia Young, who wrote in a Nov. 7 note to clients that she thinks "it's probably fair to keep expectations low."