For the third time this yr, a affected person handled with a Sarepta Therapeutics gene remedy has died, a revelation that comes as the corporate tries to earn again affected person and investor belief amid a collection of security setbacks.
The first two fatalities have been teenage boys handled with the commercialized Duchenne muscular dystrophy gene remedy Elevidys. The most recent fatality was a 51-year-old man who acquired SRP-9004, an experimental gene remedy for limb-girdle muscular dystrophy 2D/R3. All three sufferers died after creating acute liver failure.
BioCentury first reported the most recent fatality late Thursday. Sarepta confirmed the event, then held a convention name on Friday, throughout which monetary analysts peppered executives with questions on why they didn’t disclose the fatality Wednesday, when the corporate introduced a cash-saving company restructuring that features chopping 36% of its workers and stopping additional growth of two limb girdle packages, together with SRP-9004.
Sarepta CEO Doug Ingram defended the corporate’s stage of disclosure, telling analysts that the fatality was not a cloth occasion nor was it central to the subjects mentioned Wednesday. He added that the corporate’s resolution to not proceed with the 2 limb-girdle packages was monetary, and was made impartial of the fatality. Ingram defined that there was no additional dosing within the limb-girdle examine, so the correct technique to focus on the fatality can be within the presentation of the complete examine outcomes, which Sarepta plans to do at a future medical assembly.
“As pertains to materiality, definitely if there was a cloth change within the security sign of one among our marketed therapies, we might disclose that publicly,” Ingram mentioned. “I believe now we have, I consider, a really laudable historical past of being terribly clear, not solely with the doctor and affected person neighborhood, however with our investor base as properly.”
Louise Rodino-Klapac, the corporate’s head of R&D and chief scientific officer, mentioned the deceased limb-girdle affected person was a 51-year-old, non-ambulatory man. The demise occurred a month in the past, about 11 weeks after dosing. Rodino-Klapac mentioned Sarepta notified the FDA first in regards to the life-threatening liver complication, then in regards to the demise.
“The FDA was correctly knowledgeable alongside the way in which of this case,” she mentioned.
One other analyst requested whether or not Sarepta is conscious of some other fatalities related to its gene therapies. Rodino-Klapac replied no.
Regardless of Ingram’s rationalization, analysts and traders see the developments with SRP-9004 as materials and related to the corporate and to Elevidys. Sarepta’s gene therapies are delivered to their locations within the physique aboard adeno-associated viruses (AAV). Hostile reactions are a recognized threat of genetic medicines that use these engineered viruses. In a analysis observe, Leerink Companions analyst Joseph Schwartz famous that the AAV vector used for SRP-9004 is similar one utilized in Elevidys. It’s additionally utilized in SRP-9003, a Sarepta gene remedy candidate for one more type of limb-girdle muscular dystrophy. Sarepta plans to file an software later this yr looking for FDA approval of SRP-9003.
William Blair analyst Sami Corwin mentioned in a analysis observe that given the deceased limb-girdle affected person’s age, the excessive dose of the AAV-based gene remedy was the probably explanation for the liver failure. She mentioned this fatality might result in larger scrutiny of SRP-9003. It might additionally amplify hesitancy of Duchenne sufferers to make use of Elevidys and improve investor mistrust because of the failure to reveal the demise, she mentioned.
Elevidys initially gave the impression to be brilliant spot in Sarepta’s shakeup. The corporate mentioned Wednesday that the FDA requested for a label replace to incorporate a black field warning, which analysts interpreted as constructive as a result of it suggests the product gained’t be pulled from the market. However Elevidys may not be obtainable to Duchenne sufferers for much longer. The FDA will ask Sarepta to cease all shipments of the gene remedy, Reuters reported Friday afternoon, citing an unnamed supply accustomed to the matter. The FDA has been investigating the fatalities related to Elevidys, an inquiry it introduced in late June following the report of the second demise.
Picture: Michael Nagle/Bloomberg, by way of Getty Pictures
