Last week, Sarepta Therapeutics ( SRPT) on the 3Q earnings call provided key updates on SRP-9001 gene therapy in Duchenne Muscular Dystrophy (DMD). Where they already met the FDA and resolved the FDA’s requests with regard to the potency assays for the commercial material to be used in the next studies, and they came with a quick solution that the FDA agreed on.
This is the first point that the market didn’t get and appreciate the quick solution, I see it as a very positive step to get the FDA clearing SRPT’s potency assay approach, and give the green light to start dosing patients with the commercial material.
This study will be called Study-103, an open-label study in up to 10 patients, to validate the commercial material, and as $SRPT’s CEO Doug Ingram said at the conference call, this potentially more efficient way of getting a similar answer to an interim analysis as originally planned in the confirmatory phase-3 Study-301.
The second point is the new plan with Study-103, will let SRPT get the data needed, and faster than the original plan, where SRPT planned bridging Phase-3 Study-301 interim analysis from the first 10 patients as well.
So, by initiating Study-103 by year end 2020, using a multi-center study that will be able to enroll all 10 patients needed rapidly, and after 3 months follow-up and biopsy, SRPT will get the safety and microdystrophin expression data during 1Q-2021. The data collected will be used to be compare against the data from Study-102 (placebo controlled Phase-2 study in 41 patients with 48-weeks follow up) that should be ready early 1Q-2021 (even before the Study-103 readout) ) where SRPT used Nationwide Hospital’s clinical-grade drug.
The third point is that the start of Phase-3 Study-301 will be very soon after Study-103 readout, but we won’t be bothered with the Study-301 start and end date IF the FDA agrees to the bridging study & gave SRPT the green light to submit BLA for FULL APPROVAL, if Study-102 data were a clear cut & with statistical significance versus the placebo arm, and Study-103 show comparability to the NCH clinical-grade material!
On the other hand, the Phase-3 Study-301 will be mostly important to secure global approvals (Europe and the rest of the world) and additional confirmatory data.
My timeline would be
- Starting Study-103 early December & with 2 clinical sites, they can dose all 10 patients by 12/31-2020 to max 01/15/2021.
- Waiting 3 months for biopsy will take us to 03/31 to 04/15/2021
- Request FDA meeting to occur within 30 days: around 04/31 to 05/15/2021
- FDA meeting held and waiting for the official meeting minutes in 30 days: 05/31 to 06/15/2021
- Assuming the FDA like the data and ask SRPT to file BLA; then SRPT need at least 60 days to submit the BLA; take us to 07/31 to 08/15/2021
- FDA Acceptance within 60 days, around 09/31 to 10/15/2021
- PDUFA and approval +6 months (priority review total 8 months from the application submission): around 3/31/22 to 04/15/2022
This timeline hinges first of all on a positive Study-102 data and Study-103 comparability in a way they don’t give the FDA any way to say no, go with full Phase-3, but give them all the answers needed to support the AVXS’s pathway & let SRPT submit for full approval.
Assuming positive functional results from Study-102 – microdystrophin would then be a “validated surrogate endpoint” which means SRPT should get a full approval. Remember that AVXS (bought out by Novartis) got full approval for their SMA1 gene therapy, and NOT an accelerated approval.
My timeline calculation might be a slightly aggressive, so for a moderate view and taking the COVID-19 pandemic into account, you can add overall 1 to 3 months to my timeline!
Disclosure: Author is LONG SRPT