Hi kjt1969
Firstly, Sarepta now has two other drugs approved by the FDA, which are also indicated for DMD, but for different subgroups.
To your question of what I draw from the example of Exondys 51.....?
The first would be the lesson that the pathway for drugs is rarely smooth – Exondys 51 was knocked back by the FDA Advisory Committee, then approved by the FDA contrary to the predictions of "experts", but then knocked back by the EMA. The only certainty in drug development is uncertainty.
The second is that, with respect to what is deemed to be acceptable efficacy data for rare disease drugs with no available treatments, the FDA has shown that it can be highly flexible. In my view, trofinetide will come before the FDA in a much stronger position that Exondys 51. Unlike Exondys 51, the NDA submission for trofinetide in Rett will provide exactly what the FDA has requested. Trofinetide will have significantly more data, generated in many more patients, demonstrating clearer efficacy. Therefore, imo, FDA rejection of trofinetide, on the grounds of failure to prove efficacy, is highly improbable.
With respect to adverse events, I note that a high rate of vomiting and balance problems didn’t stop the FDA approving Exondys 51. Therefore, I don’t anticipate that diarrhoea (which was subsequently controlled once anti-constipation meds could be adjusted post-trial) will stand in the way of trofinetide’s approval.
The approval of Exondys 51 highlights the importance of patient community support, not only with respect to regulatory approval, but also for sales post-approval. Exondys 51 was assisted by a high level of patient community support. I believe that trofinetide shares that privilege.
The case of Exondys 51 also highlights that rare disease drugs can be extraordinarily expensive. It will be for Acadia to decide the pricing of trofinetide. I would be appalled if they priced trofinetide on a par with Exondys 51. But the fact that Exondys 51 has been a commercial success, despite its stratospheric pricing, suggests to me that Acadia pricing trofinetide even in the US$100,000+ range is unlikely to be a deterrent to payers.
Having the support of specialist physicians to prescribe your drug is clearly also important. I’m not sure what the physician support rate is for trofinetide, but I expect that it would at least equal Exondys 51’s 70% rate.
I was reminded that one should exercise caution when predicting sales, especially early sales which are exceedingly difficult to predict. In this case, Sarepta significantly underestimated first year sales. Nor were most analysts right in their predictions. That said, I’ve also seen new drug sales that massively underperformed company and analyst expectations and that probably happens more frequently than outperformance.
Finally, the case of Exondys 51 strengthens my confidence that trofinetide is destined for success.
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