Sarepta Faces Setback as Third Patient Dies in Gene Therapy Trials

Sarepta Therapeutics, a leading biotechnology company, has reported a third patient death related to its gene therapy programs, raising concerns about the safety of its treatments and potentially impacting the company's future direction.

Patient Death and Safety Concerns

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 (DMD) treatment, Elevidys.

This latest incident marks the third death associated with Sarepta's gene therapies, all of which use adeno-associated virus (AAV) vectors. The company had previously attributed the fatal liver complications to the AAV delivery system.

In response to the earlier deaths, Sarepta had already implemented several safety initiatives, including organizing an independent expert panel to assess an updated immunosuppressive regimen for patients and pausing Elevidys shipments for non-ambulatory patients. The company also added a boxed warning to Elevidys' label for acute liver injury and acute liver failure.

Corporate Restructuring and Pipeline Changes

The news of the third patient death comes on the heels of Sarepta's announcement of a significant corporate restructuring. The company plans to:

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

Despite these changes, Sarepta still intends to submit an application to the FDA for SRP-9003, another gene therapy for LGMD, in the second half of this year. This therapy uses the same AAVrh.74 delivery tool as Elevidys and the now-suspended SRP-9004.

Market and Investor Reaction

The revelation of the third patient death has had a significant impact on Sarepta's stock price, with shares down 27% in pre-market trading. This sharp decline contrasts with the 20% surge the company experienced following its restructuring announcement earlier in the week.

Analysts have expressed concern about the potential implications of this latest death. William Blair noted that the incident "could amplify patient hesitancy to use commercial Elevidys and increase investor distrust," particularly as the company did not disclose the event during its recent corporate update call.

The news has also raised questions about the risk-benefit profile of gene therapies for different muscular dystrophies. Leerink Partners analyst Joseph Schwartz pointed out that while both Duchenne and limb-girdle cause progressive loss of muscle function, Duchenne is "generally more severe," which could affect the balance of treatment risks and benefits for the two conditions.

As the pharmaceutical industry continues to grapple with the challenges and potential of gene therapies, Sarepta's experience underscores the critical importance of safety monitoring and transparent communication in the development of these cutting-edge treatments.