Sarepta plans meeting with FDA about Duchenne gene therapy
Getting Closer
Sarepta Therapeutics reported study results that showed that a commercial-grade version of its gene therapy for Duchenne muscular dystrophy seems to be comparable to the product the biotech company used in earlier clinical testing. According to BioPharma Dive, the first 11 patients to receive the commercial version of the therapy produced an average of 55.4 percent of normal levels of "micro" dystrophin — a shortened form of the protein Duchenne patients lack — three months after treatment. In an earlier trial that number was only 51.7 percent for a group of 11 patients. There were no new safety issues.
Sarepta intends to meet with the Food and Drug Administration (FDA) to determine the next steps for its program. The company hopes to design a Phase 3 study with the commercial material, but there are still key questions, such as whether disappointing Phase 2 results reported in January were simply bad luck, as Sarepta has said. Sarepta hoped that the most recent disclosure was one of the last steps before seeking the first approval for a gene therapy for Duchenne muscular dystrophy.
In 2020, CEO Doug Ingram said Sarepta intended to combine results from a Phase 2 placebo-controlled trial of the therapy, known as SRP-9001, with proof that a commercial-grade form of its therapy was just as effective as the clinical product. He believed that a combination of the two could be enough to support an FDA application while running a larger, confirmatory Phase 3 trial with the commercial product at the same time.
However, in January, SRP-9001 failed to achieve its main goal in the Phase 2 trial. While patients aged 4- to 5-years old experienced statistically significant improvements in motor function compared to those who received placebo, those between 6 and 7 years did not. The results raised doubts about Sarepta's therapy 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,” BioPharma Dive reported. Because of Sarepta’s setback, competitive programs from Pfizer and Solid Biosciences had a chance to gain ground. Sarepta's share price fell by half when the January results were announced, and it went down further since then.
Analysts think that Sarepta can succeed. The most recent findings showed that the amount of microdystrophin produced by 11 patients who received Sarepta’s commercial product was comparable to results from earlier testing. Additionally, there were no signs of the immune responses that have been seen in other Duchenne gene therapy programs.
Louise Rodino Klapac, Sarepta's senior vice president of gene therapy, said that the result indicates "consistency across our clinical and commercially representative process material." on a conference call. Brian Skorney, an analyst at Baird, said, "[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."
According to Ingram, Sarepta intends 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 discussions will be critical because of the stricter stance the FDA has taken toward gene therapy recently. Pfizer delayed U.S. patient enrollment into a Phase 3 study of its Duchenne gene therapy because of an FDA request for additional lab tests. Ingram expects to move as quickly as possible to enroll people in the next study if all goes well.
Sarepta claimed its Phase 2 study did not succeed, because some placebo recipients had milder disease, skewing the results. Sarepta hopes to confirm that hypothesis later this year, when delivering data from placebo patients who eventually switched to the gene therapy, and vice versa. Sarepta also plans to refine its Phase 3 trial design. Data from the Phase 3 study could support approvals in the U.S. and abroad.
Ingram concluded, "We've gained an enormous amount of insight and feel very confident about the probability of success of that study." Meanwhile, Sarepta shares climbed by 13 percent after the most recent news.