- Sarepta Therapeutics on Tuesday disclosed results from a small but important study, showing a commercial-grade version of its gene therapy for Duchenne muscular dystrophy appears comparable to the product it used in earlier clinical testing.
- The first 11 patients to receive the commercial version of the therapy produced an average of 55.4% of normal levels of "micro" dystrophin — a shortened form of the protein Duchenne patients lack — three months after treatment. That number was 51.7% for a similar group of 11 patients in an earlier trial. No new safety concerns were reported.
- Sarepta plans to meet with the Food and Drug Administration to determine the next steps for its closely watched program, including the design of a Phase 3 study with the commercial material. But the biotech still has key questions to answer, most notably whether disappointing Phase 2 results reported in January were simply bad luck, as the company has contended.
Sarepta had planned for its disclosure Tuesday to be one of the last steps before seeking the first approval for a gene therapy for Duchenne muscular dystrophy.
Last year, CEO Doug Ingram said the company aimed to pair results from a Phase 2 placebo-controlled trial of the treatment, known as SRP-9001, with proof that a commercial-grade form of its treatment was just as potent as the clinical product. A combination of the two, he claimed, might be enough to support an FDA application while a larger, confirmatory Phase 3 trial with the commercial product was run in parallel.
But those plans took a big hit in January, when SRP-9001 missed its main goal in the Phase 2 trial. Patients aged 4- to 5-years old experienced statistically significant improvements in motor function compared to those who received placebo, but those between 6 and 7 years didn't.
The findings raised doubts about Sarepta's program as well as about the idea underlying current Duchenne gene therapies, that delivering a gene encoding for shortened dystrophin can change the course of disease. The setback also allowed rival programs from Pfizer and Solid Biosciences to gain ground. Sarepta's share price fell by half after the results were made public, and has sunk further since.
Sarepta still has a chance to succeed, however, if several pieces fall into place. The first came Tuesday, as Sarepta showed the amount of microdystrophin produced by 11 patients who received its commercial product was comparable to results from earlier testing. Importantly, there were no signs of the immune responses that have been observed in other Duchenne gene therapy programs.
The result is indicative of "consistency across our clinical and commercially representative process material," Louise Rodino Klapac, Sarepta's senior vice president of gene therapy, said on a conference call.
"[I]nvestor confidence in the ability of SRP-9001 to consistently induce meaningful levels of microdystrophin expression should build on the heels of these results," wrote Brian Skorney, an analyst at Baird, in an investor note.
Ingram said the company plans to meet with the FDA by the middle of the year to discuss the latest results and the design of the coming Phase 3 study. The outcome of those discussions will be crucial given the seemingly stricter stance the agency has taken toward gene therapy over the past year. Pfizer, for instance, recently delayed U.S. patient enrollment into a Phase 3 study of its Duchenne gene therapy due to an FDA request for additional lab tests.
"If all goes well," Ingram said, "I promise you, we'll be moving as fast as possible to enroll that study."
Sarepta still has to prove its gene therapy actually works, too. Sarepta has claimed its Phase 2 study didn't succeed because some placebo recipients had milder disease, skewing the results. The company hopes to confirm that hypothesis later this year, when it delivers data from placebo patients who eventually switched to the gene therapy, and vice versa. The company also plans to refine its Phase 3 trial design.
The company expects it will need data from the Phase 3 study to support approvals in the U.S. and abroad, according to a Sarepta spokesperson.
"We've gained an enormous amount of insight," Ingram said on the call, and "feel very confident about the probability of success of that study."
Sarepta shares climbed by as much as 13% in early trading Tuesday.