Sarepta CEO: “We believe we have a very commendable history and are very transparent”
The patient who received Sarepta Therapeutics gene therapy for the third time this year has died, a revelation revealed as the company attempts to restore a series of safety setbacks to patients and investor trusts.
The first two deaths were teenage boys treated with commercialized duchenne muscle dystrophy gene therapy. The latest death was a 51-year-old man who received SRP-9004, an experimental gene therapy for limb muscular dystrophy 2D/R3. These three patients died after acute liver failure.
Bioustury reported the latest death toll late Thursday for the first time. Sarepta confirmed the development and then held a conference call on Friday, during which financial analysts provided executives with questions about why they did not reveal their deaths on Wednesday, when the company announced a money-saving company restructuring that included reducing its workforce by 36% and halting further development of two Limb Girdle plans, including SRP-9004.
Sarepta CEO Doug Ingram defended the company's disclosure level, telling analysts that death was not a major event or the core of the topic discussed Wednesday. He added that the company's decision not to engage in two physical bondage programs was financially and independent of death. Ingram explained that there are no further doses in the limb bundle study, so the correct way to discuss death is to show complete results, which Sarepta plans to be conducted at a future medical conference.
“It’s about materiality, of course, if there’s a significant change in the safety signal of a market therapy, we’ll disclose that publicly,” Ingram said. “I think we have a very transparent history, not only with the physician and patient community, but with our investor base.”
The deceased limb ties were a 51-year-old non-focused man, said Louise Rodino-Klapac, head of research and development and chief scientific officer of the company. The death occurred one month ago, about 11 weeks after administration. Sarepta first notified the FDA about life-threatening liver complications, followed by death, Rodino-Klapac said.
“The FDA was properly notified during the process of this case,” she said.
Another analyst asked Sarepta if it was aware of any other deaths related to its gene therapy. Rodino-Klapac answered no.
Although Ingram's explanation is explained, analysts and investors regard the development of SRP-9004 as material and is related to the company and Elevidys. Sarepta's gene therapy is delivered to in vivo destinations on adeno-associated virus (AAV). Adverse reactions are known risks of using genetic drugs for these engineered viruses. Joseph Schwartz, an analyst at Leerink Partners, noted in a research note that the AAV vector used for SRP-9004 is the same as the AAV vector used in Elevidys. It is also used in SRP-9003, another form of Sarepta gene therapy candidate for limb muscular dystrophy. Sarepta plans to submit an application later this year to seek FDA approval of SRP-9003.
Given the age of deceased limb bundle patients, high doses of AAV-based gene therapy may be the cause of liver failure, William Blair analyst Sami Corwin said in a study. She said the death could lead to a more stringent scrutiny of SRP-9003. She said that due to the failure to disclose death, it could also expand Duchampian patients' use of leverdys and increase investor distrust hesitation.
In Sarepta's reshuffle, Everidys seemed to be the highlight at first. The FDA asked for a tag update to include a black box warning that was considered positive because it indicated that the product would not be withdrawn from the market, the company said Wednesday. But Duchenne patients may not be able to use Elevidys for longer. Reuters reported on Friday afternoon that the FDA will ask Sarepta to stop all shipments of gene therapy, citing an unnamed source familiar with the matter. The FDA has been investigating the deaths related to Evandis, which was announced in late June after a second death report.
Photo: Michael Nagle/Bloomberg, by Getty Images
