Sarepta stops stopping muscle dystrophy gene therapy after the second patient dies
A patient died after receiving gene therapy for Duchenne muscle dystrophy approved by Sarepta Therapeutics, the second death the company has reported in the past three months. Like the first patient, the latest death was in the case of acute liver failure.
In addition to revealing the latest patient deaths on Sunday, Sarepta said it is developing new safety measures to mitigate the risk of liver damage to Elevidys in patients treated with gene therapy. Meanwhile, the Cambridge, Massachusetts-based company is suspending treatments for patients whose disease has reached the stage where it cannot walk. Both patients who died were non-limb.
Duchenne is a rare genetic disease in which patients lack sufficient amounts of muscle protein dystrophy protein. The disease mainly affects boys. Deterioration of muscle function can steal the patient’s ability to walk. The effect of the disease on the heart and lungs can often lead to the patient in his 20s or 30s.
Evedys uses engineered viruses to deliver a version of a gene that acquires muscle cells to produce smaller dystrophin protein muscular nutrients. Excessive immune responses are known risks of engineered viruses used to provide genetic drugs. This risk can be mitigated with drugs that inhibit such reactions. The dose of grade A is based on the patient’s weight – older and higher weight patients require higher doses. This is important because higher doses mean higher contact with engineered viruses, which in turn increases the risk of adverse reactions.
Sarepta said it is gathering a group of independent Duchenne and Lever Health experts to consider an enhanced Elevidys immunosuppressive regimen. The company proposed a therapy that includes Sirolimus, an immunosuppressant that was first approved in 1999. Sarepta proposes the use of Sirolimus based on preclinical data to show that the drug can moderately increase liver enzyme levels. Expert recommendations will be shared with the FDA; any changes to the Elevidys program will depend on what the regulator says.
Sarepta also has other recognized Duchenne therapy, administered as antisense oligonucleotides for chronic therapy. Overall, the three products had revenues of $967.1 million last year, with sales up 2% the previous year. Evedys quickly became the best product for Sarepta. The company reported Elevidys revenue in 2024 was $820.8 million, up from $200 million that entered the market in 2023.
Evedys received accelerated FDA approval in 2023, but subsequently failed to pass a confirmatory clinical trial later that year. In a controversial decision, Peter Mark, then director of the Center for Biologics Evaluation and Research (CBER), vetoed FDA staff and obtained full regulatory approval for patients who are fully walkable among patients aged 4 and older. In patients aged 4 and older who are unable to walk, the decision is accelerated approval and confirmatory studies are still required.
Sarepta voluntarily suspended a placebo-controlled confirmatory study that is enrolling non-bedded and non-focused patients in the U.S., and the company said the FDA is consistent with the step that will allow revisions to clinical trial protocols to include an enhanced immunosuppressive therapy regimen to include non-immunotherapy-based non-resistant drugs.
Accelerated approval among non-limb patients has been a debate given the lack of data in this patient population. He said the second death of non-focused patients allowed the FDA to remove these patients from the market to a larger amount of treatment, representing half of all Duchenne patients. Paradoxically, this may increase the need for outpatients as parents are no longer eligible for treatment. Schwartz said the risk/benefit profile of levidys remains relatively intact for young bedridden boys, given Duchenne’s lack of disease improvement options.
“But this will lead to another reputation for Everidys, and we want to know how demand in the outpatient space is affected,” he said. “In addition, we are now seeing increased regulatory risks, especially with CBER Director Vinay Prasad, who was previously a voice critic of Everidys’ acknowledged.”
William Blair analyst Sami Corwin said in a research note that the death of the second patient could widen investors’ concerns about the potential removal of Class A animals from the market. However, implementing a modified immunosuppressive regimen may prevent future complications from non-focusing on patients, and William Blair believes that updated tags to reflect the risk of liver injury are more likely. Corwin noted that on the label of Novartis gene therapy Zolgensma, severe liver injury and acute liver failure were marked in the black box warning, and that the increase in 2021 did not affect sales.
Leerink’s Schwartz said in another study that the development of Elevidys could open up opportunities for solid biological science. Solid Bio’s gene therapy candidate SGT-003 is designed to improve safety and efficacy. Using lower doses, the therapy is able to achieve higher levels of micropneumonia expression. Schwartz added that SGT-003 has the potential to be the only Duchenne gene therapy without immunosuppression.
“if [Sarepta] Need to add Silorimus to their dosing regimen, then [Solid Bio] It may be the only option for patients who want to avoid or are unable to accept immunosuppression. “He noted that Regenxbio’s gene therapy regimen uses both eculizumab and Sirolimus.
Sarepta Therapeutics photos
