- Sarepta Therapeutics on Monday presented new results from a placebo-controlled study of its experimental gene therapy for Duchenne muscular dystrophy, a closely watched treatment that has produced mixed results so far in clinical testing.
- The data come from 21 "crossover" patients, between five and eight years old, who initially received placebo in the Phase 2 trial and then got Sarepta's treatment the following year. Those patients scored two points better on a test of motor function after 48 weeks than observed in a historical control group over a similar time period. Importantly, no new safety concerns emerged.
- The results have emboldened Sarepta to discuss with regulators the "possibility" of seeking an approval before its Phase 3 study produces results, CEO Doug Ingram said. But they nonetheless came in below analyst expectations, sending Sarepta shares down by as much as 17% Monday.
Sarepta's latest update is important for both its therapy and for the broader field of Duchenne gene therapy research.
Results from early studies testing Sarepta's therapy, as well as similar treatments from Pfizer and Solid Biosciences, have shown each can help Duchenne patients produce a shortened form of the shock-absorbing protein, dystrophin, that they lack. The findings raised hopes that gene therapy could change the course of Duchenne, a progressive and deadly genetic disease with no cure.
But safety concerns have since slowed Pfizer's and Solid's programs. Just last month, for instance, the FDA halted Pfizer's studies after the death of a trial participant. Sarepta's drug, meanwhile, fell short in the first part of the company's Phase 2 trial a year ago, erasing plans to seek an accelerated approval from U.S. regulators in 2021.
Sarepta blamed that disappointing result on bad luck in the patient randomization process, and said the majority of those who received its treatment got too low of a dose. The company argued further study data would prove its hypothesis and designed a Phase 3 trial with a variety of adjustments meant to boost its odds of success. Enrollment in that study, called Embark, should finish by the middle of the year, with results expected in 2023.
Sarepta CEO Ingram has repeatedly said the company's "base case" is to file for approval should the Embark results prove positive. But Ingram has left the door open for a quicker path to market, if the data from the second half of its Phase 2 study — what Sarepta disclosed Monday — were good enough.
In its analysis, Sarepta compared trial volunteers who were switched from placebo to treatment to patients in an separate control group, matched by factors like age and disease severity. The idea was to develop a comparison "with such rigor" that could be used to support an approval filing, Ingram said during a presentation at the J.P. Morgan Healthcare Conference on Monday.
Among the treated patients, Sarepta reported an average 1.3-point increase on a standard test of motor function, versus a projected 0.7-point decline for the control group. The improvement was observed in kids who were just over 7 years old at the start of the trial. Natural history suggests those children are at the beginning of "what will become a very significant decline," Ingram said.
Patients who were treated earlier had results that were stable for two years as well.
"The data look supportive, albeit not definitive," wrote Brian Abrahams, an analyst at RBC Capital Markets, in a note to clients. The findings likely add to confidence in those who believe the treatment works, but aren't compelling enough to "convince doubters," he added.
The improvement, however, is less than the roughly 3-point difference Sarepta saw in a small trial earlier this year. They're also below the expectations of other analysts, like SVB Leerink's Joseph Schwartz, who predicted a benefit over placebo of 2.5 to 3.5 points.
"[W]e could see investors being initially disappointed by today's results upon first glance of the numerical change," Schwartz wrote. But they're "compelling in the context of Duchenne natural history," where even a 1-point improvement on a motor function test can lead to an "observable benefit."
Sarepta, for its part, claims the findings are good enough to at least discuss "the possibility of a pathway" that would be faster than waiting for Phase 3 results, Ingram said. That meeting should take place sometime this year, though Ingram wouldn't say when.