- Sarepta Therapeutics on Monday revealed new results from clinical testing of its closely watched gene therapy for Duchenne muscular dystrophy and outlined the design of the key trial that could eventually support its approval.
- The new results showed 11 patients treated with Sarepta's drug six months ago exhibited improvements on a test of their motor function when history suggests they should have declined. One serious immune reaction involving muscle weakness was reported as well, however, which Sarepta attributed to the patient's underlying genetics. Shares fell 5%.
- The Phase 3 study known as EMBARK, meanwhile, will include 120 participants between the ages of 4 and 7. Sarepta will stratify study volunteers by their age and condition at the start of the trial, a plan it hopes will lead to better results than it observed in Phase 2 testing.
Sarepta and rival Pfizer are neck and neck in a race to bring gene therapy to Duchenne, a progressive and fatal genetic disease. Both have started Phase 3 trials, though only Sarepta has been cleared to begin late-stage testing in the U.S.
Both have also had setbacks. In January, Sarepta's gene therapy fell short in the first part of a Phase 2 trial, erasing previous plans for an approval filing this year along with half the company's value. And last month, Pfizer reported two patients experienced a type of heart inflammation in clinical testing so worrisome that the company now aims to exclude people with certain genetic traits — a group covering about 15% of Duchenne patients — from its Phase 3 study.
Sarepta, for its part, blamed its lack of success in the Phase 2 study on bad luck in the patient randomization process. Patients aged 4 to 5 years old experienced statistically significant improvements in motor function compared to those who received placebo, while those between 6 and 7 years didn't. Sarepta argued some patients who received placebo had milder disease, skewing the results.
Sarepta now has the chance to prove that theory. On a conference call with analysts Monday, Sarepta outlined the path forward for its treatment, starting with crucial data from placebo patients who eventually switched to the gene therapy in the Phase 2 trial, and vice versa. Sarepta may aim for an accelerated approval filing if those results are "compelling," CEO Doug Ingram said.
Specifically, Sarepta will decide whether "the totality of the evidence" the biotech will have accrued by then justifies those conversations, Ingram said. Some of that evidence was disclosed Monday afternoon and showed the first 11 patients who received its treatment in a small trial had a 3-point average increase on a standard test of motor function. History suggests those patients, aged 6 to 7, were expected to decline by 0.5 points on that test, the company said.
That finding was one of a few comparisons to so-called historical controls that Sarepta used on Monday to prove its treatment may change the trajectory of Duchenne. Overall, they "support [the treatment's] likely benefit," wrote RBC Capital Markets analyst Brian Abrahams, “though with the caveats that come with cross-trial comparisons.”
Indeed, Sarepta's “base case assumption” is that it will need positive results from the placebo-controlled Phase 3 trial to win approvals in the U.S. and elsewhere, Ingram said. Aiming to boost its odds of success, Sarepta is ensuring at least half of the patients enrolled will be 4 or 5 years old and have certain baseline characteristics that ensure a more “homogenous trajectory," said Louise Rodino-Klapac, Sarepta's executive vice president and chief scientific officer. Sarepta aims to have the study fully enrolled by the middle of 2022 and to report results the following year.
Still, Sarepta shares slumped 5%, which analysts attributed to the disclosure of a single immune-related side effect investigators classified as severe. Like Pfizer reported in September, Sarepta said the trial participant experienced muscle weakness after treatment, and cited certain underlying genetic traits. The finding points to a "class effect" for the Duchenne gene therapies, Abrahams wrote.
Like Pfizer, Sarepta aims to mitigate the problem by excluding some patients from its Phase 3 test. But Sarepta believes the group includes less than 3% of Duchenne patients, Rodino-Klapac said.