Sarepta Therapeutics announced Monday that its pivotal nine-year clinical trial testing two gene-targeted therapies for Duchenne muscular dystrophy failed to meet its primary endpoint, triggering a sharp decline in the company's stock price of over 37% in extended trading.
The study enrolled 225 boys aged 6 to 13 with a rare form of Duchenne muscular dystrophy that can be treated by skipping exons 45 or 53. The trial evaluated casimersen and golodirsen, which belong to a class of drugs called phosphorodiamidate morpholino oligomers (PMOs) that help patients produce functional dystrophin protein.
Primary Endpoint Results
While patients demonstrated numerical improvement in climbing four steps after 96 weeks of treatment, the difference failed to reach statistical significance. Sarepta reported an observed difference of 0.05 steps per second on the primary endpoint, falling short of the threshold needed to demonstrate clinical benefit.
The company attributed part of the trial's challenges to the COVID-19 pandemic, which disrupted trial participation and data collection throughout the study period. "The COVID-19 pandemic disrupted trial participation and data collection, adding complexity to the study and potentially affecting the results," the company stated.
Secondary Analysis Shows Promise
Despite missing the primary endpoint, Sarepta highlighted encouraging trends in secondary analyses. When excluding COVID-affected patients, the therapies demonstrated a 30% reduction in disease progression. Long-term data revealed that treatment delayed the need for wheelchair use by nearly three years, a clinically meaningful outcome for patients and families.
J.P. Morgan analyst Anupam Rama noted, "we do see a fairly clear rationale for the miss (COVID)" and pointed to supportive trends when excluding pandemic-affected patients.
Safety Profile and Regulatory Path Forward
The therapies maintained a favorable safety profile throughout the extended trial period, with Sarepta reporting that the treatments were well tolerated with no new safety concerns identified. This safety data supports the company's confidence in pursuing regulatory discussions.
Despite the primary endpoint failure, Sarepta plans to meet with the U.S. Food and Drug Administration to discuss converting the drugs' current accelerated approvals into full approvals. Company executives expressed confidence during a conference call, stating they "really do not believe that there's a risk of losing marketing authorization" given the "extraordinarily beneficial safety profile."
Rama added cautious optimism: "We do see strong rationale for potential full approval," while noting that "regulatory processes can be a wild card in the current environment."
Disease Context and Market Impact
Duchenne muscular dystrophy is a rare genetic disorder that causes progressive muscle weakness and primarily affects boys. The condition typically begins in early childhood and worsens over time, making walking, breathing, and other daily activities increasingly difficult for patients.
The trial results represent another setback for Sarepta, which has faced significant challenges this year. The company has lost approximately 80% of its market value as mounting regulatory scrutiny and three patient deaths linked to its separate gene therapy, Elevidys, have triggered clinical trial holds and raised concerns about the company's safety oversight.
Sarepta indicated it expects to finalize safety labeling discussions with the FDA soon, likely resulting in a boxed warning and removal of non-ambulatory use from Elevidys' label. These regulatory challenges underscore the complex landscape facing the company as it navigates multiple product development programs in the rare disease space.
