Sarepta's DMD gene therapy gains label expansion

Sarepta Therapeutics’ gene therapy Elevidys (delandistrogene moxeparvovec-rokl) is now accessible to more patients with Duchenne muscular dystrophy (DMD). The FDA recently expanded its approval to include both non-ambulatory boys and those aged four years and older. Previously, the gene therapy was only approved for ambulatory patients between four and five years old. Importantly, the new approval did not impose an upper age limit, although clinical trials primarily involved boys no older than seven. This development led to a significant rise in Sarepta’s stock, which surged over 35% during after-hours trading.

Sarepta had been advocating for a more inclusive age range after the FDA’s initial decision found the efficacy in older patients unconvincing. The agency had decided to wait for additional data from the ongoing Phase III EMBARK study, which included boys up to age seven. Despite Elevidys missing the primary endpoint in the EMBARK study, the broadening of its label was still anticipated. Although the drug did not show a significant improvement in the North Star Ambulatory Assessment (NSAA) total score compared to placebo after 52 weeks, it did meet several key secondary endpoints. These included improvements in time to rise, 10-meter walk test, time to ascend four steps, and creatine kinase levels.

The FDA, in its approval letter, highlighted that the observations from the secondary and exploratory endpoints indicated a clinical benefit compared to placebo. Jonathan Strober, a professor of neurology at UCSF Weill Institute for Neurosciences, had predicted the FDA would eventually widen Elevidys’ label due to the limited treatment options available for patients and their families. Strober’s perspective seemed to resonate with the FDA’s rationale, which took into account the life-threatening and debilitating nature of DMD and the urgent unmet medical need.

Elevidys’ favorable position is further strengthened by the lack of other gene therapy alternatives. Pfizer’s fordadistrogene movaparvovec, a potential competitor, recently failed its Phase III DMD study, leaving Sarepta without immediate competition. This situation offers Elevidys a clear path in the market, as patients have fewer treatment options.

The demand for DMD treatments has significantly boosted Elevidys’ uptake, despite the initially narrow label. In 2023, Elevidys generated full-year sales of $200.4 million, with $131.2 million earned in the fourth quarter alone, exceeding both internal and external expectations. Sarepta has yet to provide revenue projections for 2024, pending the label expansion.

While no other gene therapy is expected to compete with Elevidys in the near future, other treatment modalities are emerging. Antibody-oligo conjugates from companies like Dyne Therapeutics and Avidity Biosciences have started to show promising results, supporting their potential in the treatment landscape of DMD.

In summary, the FDA’s expanded approval of Elevidys to include a broader patient population marks a significant step forward in the treatment of Duchenne muscular dystrophy. With limited alternatives available and strong demand for effective therapies, Elevidys is well-positioned to make a substantial impact on the lives of many patients and their families.