Sarepta Reports Third Gene Therapy-Related Death, Announces Major Restructuring

Sarepta Therapeutics, a leading pharmaceutical company in gene therapy development, has reported a third patient death related to its gene therapy treatments. This latest fatality, coupled with a significant corporate restructuring, has sent shockwaves through the pharmaceutical industry and raised concerns about the safety of gene therapies.

Patient Death in Limb-Girdle Muscular Dystrophy Trial

A 51-year-old man participating in a Phase I study for limb-girdle muscular dystrophy (LGMD) died in June after receiving Sarepta's investigational gene therapy, SRP-9004. The cause of death was acute liver failure, the same complication responsible for two previous fatalities linked to Sarepta's Duchenne muscular dystrophy treatment, Elevidys.

The company confirmed the death to BioSpace, stating, "While we do everything possible to ensure patient safety, there is inherent risk in clinical trials. Our deepest condolences go to the family and all those involved in his care."

This latest incident marks the third gene therapy-related death for Sarepta, following two previous fatalities in patients treated with Elevidys. All three deaths have been attributed to acute liver failure, a known risk associated with adeno-associated virus (AAV) vector-based gene therapies.

Corporate Restructuring and Pipeline Adjustments

In a separate announcement, Sarepta revealed plans for a major corporate overhaul. The company will:

1. Lay off approximately 500 employees, representing about 36% of its workforce.
2. Reduce its pipeline to achieve an estimated $420 million in savings.
3. Shift focus towards siRNA programs instead of gene therapies.
4. Suspend work on "most of the gene therapies in development for limb-girdle muscular dystrophy," including SRP-9004.

Despite the restructuring, Sarepta plans to continue development of SRP-9003, another gene therapy for LGMD, with plans to submit an FDA application in the second half of this year.

The company's shares initially surged 20% following the restructuring announcement. However, news of the third patient death has since led to a 27% drop in pre-market trading.

Safety Concerns and Regulatory Response

In response to the earlier Elevidys-related deaths, Sarepta had already implemented several safety initiatives, including:

1. Organizing an independent expert panel to assess an updated immunosuppressive regimen for patients.
2. Pausing Elevidys shipments for non-ambulatory patients.
3. Adding a boxed warning to Elevidys' label for acute liver injury and acute liver failure.

The recurring issue of liver complications has raised questions about the safety profile of AAV vector-based gene therapies, particularly those administered at high doses for neuromuscular conditions like Duchenne and limb-girdle muscular dystrophies.

Leerink Partners analyst Joseph Schwartz noted that while both conditions cause progressive loss of muscle function, "Duchenne is generally more severe than limb-girdle, making the balancing of treatment risks and benefits for the two conditions very different."

As the pharmaceutical industry grapples with these developments, the future of gene therapy research and development remains uncertain. Regulatory bodies, including the FDA, are likely to scrutinize gene therapy trials more closely, potentially impacting the approval process for future treatments in this rapidly evolving field.