FDA Imposes Clinical Hold on Sarepta's LGMD Gene Therapy Trials Amid Safety Concerns

The U.S. Food and Drug Administration (FDA) has placed a clinical hold on all of Sarepta Therapeutics' investigational limb-girdle muscular dystrophy (LGMD) gene therapy trials, citing serious safety concerns. This decision comes in the wake of three patient deaths potentially linked to Sarepta's gene therapies, including its FDA-approved Duchenne muscular dystrophy (DMD) treatment, Elevidys.

Safety Concerns Prompt Regulatory Action

The FDA's decision to halt Sarepta's LGMD trials stems from "three deaths potentially related to these products and new safety concerns that the study participants are or would be exposed to an unreasonable and significant risk of illness or injury," according to a July 18 release from the regulator. Two of the reported deaths occurred in patients receiving Elevidys, while the third involved a 51-year-old man with LGMD type 2D/R3 participating in a phase 1 trial of SRP-9004. All three patients reportedly died from acute liver failure.

In addition to the clinical hold, the FDA has revoked Sarepta's gene therapy platform technology designation for its AAVrh74 technology, which had been granted on June 2. This designation is typically used to expedite the FDA review process for new products stemming from the same platform.

Impact on Sarepta's Pipeline and Operations

The clinical hold affects multiple Sarepta gene therapy candidates, including SRP-9003, SRP-9004, SRP-6004, and SRP-9005. Prior to the FDA's action, Sarepta had already announced plans to discontinue development of most of its experimental LGMD gene therapies, with the exception of SRP-9003.

Sarepta had previously completed enrollment and dosing in a global phase 3 trial assessing SRP-9003 for LGMD type 2E/R4 in December 2022. The company had intended to submit a biologics license application (BLA) for FDA review in the second half of this year, potentially via accelerated approval. Despite the current hold, Sarepta still plans to discuss a potential accelerated approval pathway with the FDA once the clinical hold is lifted.

The company is now working closely with investigators to ensure continuity of care and data integrity for patients who have already been dosed in the affected studies. A Sarepta spokesperson stated, "In the studies where patients were dosed, we are working closely with investigators to ensure continuity of care and data integrity to deliver on our regulatory obligations."