Another person treated with a Sarepta Therapeutics gene therapy has died, according to reports from BioCentury and multiple other publications.
According to the publications, a 51-year-old man with limb-girdle muscular dystrophy died after treatment with the company’s experimental SRP-9004 therapy in a Phase 1 study. Earlier this year, Sarepta reported the deaths of two teenagers with Duchenne muscular dystrophy who received its marketed gene therapy Elevidys.
Sarepta did not respond to multiple attempts by BioPharma Dive to contact the company by phone and email. The company didn’t disclose the death during a restructuring announcement and conference call it held Wednesday.
Sarepta has scheduled another conference call for Friday morning to “discuss” its limb-girdle programs.
As with the deaths of the two Duchenne patients, the man with limb-girdle died after complications from acute liver failure, BioCentury and others reported. Liver damage is a known risk of gene therapies that, like Elevidys and SRP-9004, are built around a type of engineered virus. Researchers have long expressed concern the risk may be greater for gene therapies administered at high doses, which are needed to treat neuromuscular conditions like Duchenne and limb-girdle.
The two deaths related to Elevidys were the first reported among more than 900 people who had been treated with it in clinical testing and commercially as of June. Sarepta is working on a regimen of immune-suppressing drugs to help manage the safety risks in older Duchenne patients who can still walk, and plans to soon share its findings with the FDA. In the meantime, the agency placed a “black box” safety warning on Elevidys’ label for the risk of liver failure.
However, Friday’s news could indicate that Sarepta’s other gene therapy work may be associated with similar safety risks. Elevidys and SRP-9004 both use the same delivery tool, a modified virus dubbed AAVrh.74, to deliver genetic material into the body. While Sarepta plans to shelve SRP-9004 as part of its restructuring, the company intends to soon seek approval of another limb-girdle muscular dystrophy treatment, SRP-9003, that’s based on same modified virus.
Like Duchenne, limb-girdle causes progressive loss of muscle function and potentially early death from other health complications. However, Duchenne is “generally more severe” than limb-girdle, making the balancing of treatment risks and benefits for the two conditions very different, Leerink Partners analyst Joseph Schwartz wrote in a Friday note to investors.
The death “could lead to greater scrutiny of SRP-9003’s safety profile” and “affect commercial interest, if approved,” added William Blair analyst Sami Corwin, in a separate note. It may also “amplify patient hesitancy to use commercial Elevidys and increase investor distrust,” since Sarepta didn’t disclose the event earlier this week, she added.
Sarepta shares, which has jumped higher on news of the restructuring, fell by double digits in early morning trading Friday.
