A affected person has died following therapy with Elevidys, the Sarepta Therapeutics product that’s the solely FDA-approved gene remedy for Duchenne muscular dystrophy, the corporate disclosed Tuesday.
The affected person, a younger man, suffered acute liver failure after receiving the remedy, Sarepta stated. Liver harm is a recognized complication danger of Elevidys and different gene therapies that use an adeno-associated (AAV) virus to ship the one-time therapy to cells. That danger is already flagged on the Elevidys label. However acute liver harm resulting in dying has not been beforehand reported in scientific testing or real-world use of Elevidys.
Sarepta stated testing revealed the affected person who died had a current cytomegalovirus (CMV) an infection that the treating doctor recognized as a possible contributing issue to the dying. This an infection can harm the liver, resulting in CMV hepatitis, which might change into deadly in these with weakened immune methods.
In Duchenne, genetic mutations result in deficiency of a key muscle protein known as dystrophin. This uncommon illness, which impacts largely boys, results in progressively worsening muscle perform that usually robs sufferers of the flexibility to stroll by the age of 12. Declining lung and coronary heart perform can result in dying in a affected person’s 20s or early 30s.
Elevidys will get a affected person’s muscle cells to provide a smaller model dystophin. The gene remedy received accelerated FDA approval in 2023, however went on to fail its confirmatory Part 3 take a look at. Final June, Elevidys transformed its standing to full FDA approval for sufferers who can nonetheless stroll. For non-ambulatory sufferers, the remedy’s standing is an accelerated approval that requires one other confirmatory examine. The choice was a controversial one which got here solely after a high FDA official overruled company workers concerning the gene remedy’s efficacy.
In January, Sarepta reported new Part 3 outcomes displaying that members within the second a part of the two-part examine confirmed enchancment measured at one 12 months, in accordance a ranking evaluation for Duchenne sufferers. No new security alerts had been reported at the moment.
Shares of Sarepta sank about 20% following the fatality announcement Tuesday, however analysts who comply with the corporate described the investor response as overblown. William Blair analyst Sami Corwin stated in a analysis observe that that is the primary Elevidys-related dying. Fatalities have additionally been reported following the launch of Novartis’s Zolgensma, an AAV-delivered gene remedy for spinal muscular atrophy. She added that the current CMV an infection might have exacerbated the Duchenne affected person’s situation, suggesting extra security screening measures may very well be used to forestall future deaths.
The affected person’s age might have been a contributing issue, Leerink Companions Joseph Schwartz stated in a analysis observe. Older Duchenne sufferers have greater morbidity. Additionally, Elevidys is dosed based on affected person weight. An older, heavier affected person would require the next dose. Sarepta administration advised Leerink they consider this case is “very distinctive,” reiterating that is the primary fatality in additional than 800 sufferers who obtained Elevidys in scientific trials or as a prescribed remedy.
“Though we acknowledge that such extreme unintended effects related to mortality can definitely be alarming and trigger the neighborhood to query the danger/good thing about treating older sufferers, we consider that the very low total incidence which we estimate at lower than 0.125% based mostly on mixture publicity to this point is encouraging,” Schwartz wrote. “Whereas fewer non-ambulatory sufferers have been handled with Elevidys thus far (>100 since June 2024), the speed remains to be lower than 1% which might nonetheless be thought of low.”
Schwartz stated that whereas Elevidys continues to have a positive danger/profit profile, the fatality might present a elevate for corporations creating next-generation gene therapies for Duchenne. Regenxbio and Stable Biosciences use totally different capsids and transgenes of their respective gene therapies.
The upper danger for non-ambulatory Duchene sufferers seems to have precedent. In 2021, a affected person handled with an experimental Pfizer gene remedy for Duchenne died in a scientific trial, resulting in a scientific maintain. The examine enrolled ambulatory and non-ambulatory sufferers; Pfizer stated the affected person dying was within the non-ambulatory cohort. Although Pfizer was later cleared to renew testing, the gene remedy failed in Part 3. Final summer time, Pfizer discontinued this program.
Sarepta stated it has reported the fatality to well being authorities and the corporate intends to replace the prescribing data to signify the occasion. The corporate has additionally knowledgeable scientific trial investigators and prescribing physicians.
Photograph by Sarepta Therapeutics
