Sarepta Reports Third Gene Therapy-Related Death, Prompting Safety Concerns and Corporate Restructuring

Sarepta Therapeutics, a leading player in gene therapy development, has confirmed a third patient death related to its gene therapy treatments, sparking renewed safety concerns and prompting a significant corporate restructuring. This latest development comes amid a tumultuous period for the company, which has seen its stock price fluctuate dramatically in response to recent events.

Patient Death and Safety Concerns

A 51-year-old man with limb-girdle muscular dystrophy (LGMD) type 2D/R3 died in June after receiving Sarepta's investigational gene therapy SRP-9004 in a Phase 1 trial. The cause of death was acute liver failure, mirroring the complications that led to two previously reported fatalities linked to Sarepta's Duchenne muscular dystrophy (DMD) gene therapy, Elevidys.

This marks the third death associated with Sarepta's gene therapies, following the deaths of two teenage boys with DMD who were treated with Elevidys earlier this year. All three deaths have been attributed to acute liver failure, a known risk of gene therapies that use adeno-associated virus (AAV) vectors.

The company has informed regulators and clinical investigators of the death, emphasizing the inherent risks in clinical trials while expressing condolences to the patient's family. However, analysts have criticized Sarepta for not disclosing the event during its corporate update earlier this week, raising questions about transparency.

Corporate Restructuring and Strategic Shift

In response to these safety concerns and broader strategic considerations, Sarepta announced a major corporate restructuring on Wednesday. The company plans to:

1. Lay off approximately 500 employees, representing about 36% of its workforce.
2. Pare down its pipeline to achieve an estimated $420 million in savings.
3. Shift focus to siRNA programs instead of gene therapies.
4. Suspend work on most gene therapies in development for limb-girdle muscular dystrophy, with the exception of SRP-9003.

The restructuring announcement initially led to a 20% surge in Sarepta's stock price, with analysts praising the business overhaul. However, following the disclosure of the third patient death, the company's shares fell by double digits in early morning trading on Friday.

Implications for Ongoing Programs

The recent death has raised concerns about the safety profiles of Sarepta's other gene therapy candidates, particularly SRP-9003, which the company still plans to submit for FDA approval in the second half of 2025. Both SRP-9004 and SRP-9003 use the same AAV vector as Elevidys, potentially linking them to similar safety risks.

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

1. Organizing an independent panel of experts 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.

These measures, coupled with the latest patient death, may impact patient willingness to use Elevidys and affect commercial interest in SRP-9003, if approved.

As the pharmaceutical industry grapples with the challenges of gene therapy development, Sarepta's experience underscores the delicate balance between potential benefits and risks in treating rare and severe genetic disorders. The company's pivot towards siRNA programs and its ongoing efforts to address safety concerns will likely shape the future direction of gene therapy research and development.