Sarepta's Duchenne Drugs Face Setbacks in Confirmatory Trials, Company Pursues Full Approval

Sarepta Therapeutics, a leading player in the Duchenne muscular dystrophy (DMD) treatment landscape, is facing significant challenges as its key drugs fail to meet primary endpoints in confirmatory trials. Despite these setbacks, the company is pushing forward with plans to seek full approval for its treatments, citing real-world evidence and pandemic-related complications as mitigating factors.

Essence Trial Results and Implications

Sarepta's nine-year-long Essence trial, designed to confirm the benefits of exon-skipping drugs Vyondys 53 and Amondys 45, failed to meet its primary endpoint. The study did not show a statistically significant difference compared to placebo on the 4-step ascend velocity test, a key measurement of DMD patient mobility. The observed difference was 0.05 steps/second on average, with a high p-value of 0.309.

Despite this setback, Sarepta CEO Doug Ingram remains optimistic, stating, "We believe that we have met that standard and that we have sufficient evidence to discuss with the agency transitioning from accelerated to traditional approval." The company plans to meet with the FDA by the end of the year to discuss converting the accelerated approvals for Vyondys and Amondys into traditional clearances.

Elevidys Gene Therapy Developments

Sarepta's gene therapy Elevidys is also facing challenges. The company is working with the FDA to formally remove the non-ambulatory indication from the gene therapy's label following safety concerns. A label update, including a box warning about liver toxicity, is expected to be finalized soon.

Despite these issues, Elevidys generated sales of $131.5 million in the third quarter, surpassing analysts' expectations. Sarepta executives expressed confidence in the therapy's potential, with Ingram stating, "We certainly feel very comfortable about that kind of baseline concept of $500 million for Elevidys."

Market Response and Future Outlook

The series of setbacks has significantly impacted Sarepta's market position. The company's stock was trading down about 36% pre-market on Tuesday to below $15 per share, compared to around $120 at the beginning of the year.

As Sarepta navigates these challenges, it is exploring additional strategies to mitigate risks and bolster its product portfolio. The company is proposing the addition of the immunosuppressant sirolimus to address liver toxicity concerns with Elevidys and is finalizing the design of a new cohort in its Endeavor trial to demonstrate the effect of additional prophylactic immunosuppression in non-ambulatory patients.