For the third time this 12 months, 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 primary two fatalities had been teenage boys handled with the commercialized Duchenne muscular dystrophy gene remedy Elevidys. The newest fatality was a 51-year-old man who obtained 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 reducing 36% of its workers and stopping additional growth of two limb girdle applications, together with SRP-9004.
Sarepta CEO Doug Ingram defended the corporate’s degree of disclosure, telling analysts that the fatality was not a fabric occasion nor was it central to the subjects mentioned Wednesday. He added that the corporate’s determination to not proceed with the 2 limb-girdle applications was monetary, and was made unbiased of the fatality. Ingram defined that there was no additional dosing within the limb-girdle research, so the right solution to focus on the fatality could be within the presentation of the total research outcomes, which Sarepta plans to do at a future medical assembly.
“As pertains to materiality, actually if there was a fabric change within the security sign of one in every of our marketed therapies, we might disclose that publicly,” Ingram stated. “I feel we have now, I imagine, a really laudable historical past of being terribly clear, not solely with the doctor and affected person neighborhood, however with our investor base as nicely.”
Louise Rodino-Klapac, the corporate’s head of R&D and chief scientific officer, stated the deceased limb-girdle affected person was a 51-year-old, non-ambulatory man. The loss of life occurred a month in the past, about 11 weeks after dosing. Rodino-Klapac stated Sarepta notified the FDA first in regards to the life-threatening liver complication, then in regards to the loss of life.
“The FDA was correctly knowledgeable alongside the best way of this case,” she stated.
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 clarification, 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). Adversarial reactions are a recognized threat of genetic medicines that use these engineered viruses. In a analysis be aware, 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 12 months in search of FDA approval of SRP-9003.
William Blair analyst Sami Corwin stated in a analysis be aware that given the deceased limb-girdle affected person’s age, the excessive dose of the AAV-based gene remedy was the probably reason for the liver failure. She stated this fatality may result in better scrutiny of SRP-9003. It may additionally amplify hesitancy of Duchenne sufferers to make use of Elevidys and improve investor mistrust as a result of failure to reveal the loss of life, she stated.
Elevidys initially seemed to be vivid spot in Sarepta’s shakeup. The corporate stated 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 received’t be pulled from the market. However Elevidys won’t be out there 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 acquainted with 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 loss of life.
Picture: Michael Nagle/Bloomberg, by way of Getty Pictures
