Perhaps the next shoe to drop will be an announcement from Prosensa (RNA) that it will also seek FDA approval for its DMD drug drisapersen. The company has been re-analyzing data from the phase II and phase III studies conducted by old partner GlaxoSmithKline (GSK), clearly with the intent to file on its mind.
I see no reason why FDA would agree to review Sarepta's application but say no to Prosensa. Prosensa shares are up more than 50% this year, so clearly, investors are anticipating a drisapersen FDA filing as well.
To answer the next, logical question: No, I don't view a drisapersen FDA filing as negative for Sarepta or eteplirsen. The prospect of a two-day, all DMD FDA advisory panel sometime next year is incredibly exciting. I believe eteplirsen is the superior drug, so a drisapersen FDA review, even a dual approval, isn't a problem in my mind.
Douglas R. asks:
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Some background will be helpful. MM-398 wraps the "old" chemotherapy drug irinotecan in spheres of liposomes, or fats, which is supposed to increase the absorption of the drug inside tumors where it can be most effective and minimize exposure in surrounding, healthy tissue, therefore reducing potential for side effects.
The study, dubbed NAPOLI-1, enrolled pancreatic cancer patients no longer responding to treatment with gemcitabine. One third of the patients were randomized to receive MM-398 on its own. A second third of patients received MM-398 and two chemotherapy drugs -- 5FU and leucovorin. The remaining patients -- the control arm of the study -- received 5FU and leucovorin.
As reported by Merrimack, treatment with MM-398 plus 5FU/leucovorin resulted in a statistically significant, 33% reduction in the risk of death (hazard ratio 0.67) compared to the 5FU/leucovorin patients. The median overall survival in the MM-398 combination arm was 6.1 months vs. 4.2 months for the control arm -- a survival benefit of just under 8 weeks. No difference in survival was reported between the MM-398 monotherapy arm and the control patients.]
Is this study strong enough to get MM-398 approved by FDA? Merrimack bulls say yes, especially if the full data (not yet presented) match what we've seen from the company's press release. An eight-week survival benefit isnt much but would likely be deemed clinically meaningful for advanced pancreatic cancer patients who no longer respond to first-line therapy. MM-398 is the first drug to show a survival benefit in the second-line setting, where no drugs are formally approved.
The bears and skeptics say a significant risk and potential review issue for MM-398 -- maybe an interesting discussion at an advisory panel -- will be whether Merrimack gamed the design of the phase III study to boost the drug's chance for a positive result. MM-398 is reformulated irinotecan, so why didn't Merrimack compare the efficacy and safety of the two drugs in the phase III study?
I asked Merrimack CEO Bob Mulroy this question. He insists MM-398 is a novel cancer drug. It is not just a reformulation of old irinotecan, so comparing the two drugs in a clinical trial wasn't necessary.
There was no pushback or questions from the FDA or the EMEA about the control arm of the phase III study, said Mulroy. Merrimack didnt pursue a Special Protocol Assessment (SPA) for the MM-398 phase III study because overall survival is the gold standard primary endpoint, he added.
While there are no drugs formally approved for second-line pancreatic cancer, the 5FU/leucovorin combination is listed in treatment guidelines, hence Merrimack's decision to make it the control arm of the phase III study.
Yet a triple-combination therapy of 5FU, leucovorin and irinotecan known as Folfiri has been studied in first and second-line pancreatic cancer with overall survival data comparing favorably to MM-398. You can find examples of Folfiri studies here, here, here and here.