Sarepta Therapeutics said it will voluntarily “and temporarily” pause all shipments of Elevidys® (delandistrogene moxeparvovec-rokl), the marketed Duchenne muscular dystrophy (DMD) treatment linked to the deaths of two patients this year.
Sarepta’s about-face came just three days after the company refused a request from the FDA to voluntarily halt shipments of the drug for ambulant DMD patients. The company voluntarily paused shipments to non-ambulant DMD patients in June following the second patient death tied to Elevidys.
The pause will take effect at the close of business Tuesday. Sarepta hasn’t said how long it intends to temporarily halt Elevidys shipments.
“This proactive step will allow Sarepta the necessary time to respond to any requests for information and allow Sarepta and FDA to complete the Elevidys safety labeling supplement process,” Sarepta stated. The FDA has requested that Elevidys’ label include a black box warning for acute liver failure and acute liver injury, a request supported by Sarepta.
“The company looks forward to a collaborative, science-driven review process and dialogue with the FDA,” Sarepta added.
Sarepta announced the pause in a statement reversing its position from Friday, when it announced its refusal to withdraw Elevidys by saying the decision was “based on our comprehensive scientific interpretation of the data, which shows no new or changed safety signals in the ambulant patient population.”
The FDA responded to Sarepta’s initial refusal to withdraw with a statement that expressed “deep disappointment” in Sarepta—and which threatened to use the “full regulatory authority” of the agency to compel the company to halt Elevidys shipments. Earlier Friday, the FDA placed clinical holds on Sarepta’s clinical trials of its gene therapy candidates for limb-girdle muscular dystrophy.
“Productive and positive” relationship
“It is important for the patients we serve that Sarepta maintains a productive and positive working relationship with FDA, and it became obvious that maintaining that productive working relationship required this temporary suspension while we address any questions that FDA may have and complete the Elevidys label supplement process,” Sarepta CEO Douglas S. Ingram said in a statement.
“As a patient-centric organization, the decision to voluntarily and temporarily pause shipments of Elevidys was a painful one, as individuals with Duchenne are losing muscle daily and in need of disease-modifying options,” Ingram added.
The FDA acted after Sarepta on Thursday acknowledged the death of a third patient tied to one of the company’s gene therapies, SRP-9004 (patidistrogene bexoparvovec), a gene therapy candidate developed to treat LGMD Type 2D/R3, also called alpha-sarcoglycanopathy.
Sarepta shares nosedived 36% on news that a 51-year-old man with non-ambulant limb-girdle muscular dystrophy (LGMD) died last month after being dosed in the Phase I DISCOVERY trial (Study SRP-9004-102; NCT01976091). DISCOVERY is a proof-of-concept study designed to assess the safety and expression of the alpha-sarcoglycan protein following treatment with SRP-9004.
The death comes four months after Sarepta acknowledged the death of a 16-year-old young man with Duchenne muscular dystrophy following treatment with Elevidys and just over a month after the company disclosed the death of a second Elevidys patient, whose age has not been disclosed.
“The key questions are how long the pause will remain in effect, and how much of Elevidys’ adoption in ambulatory DMD will ultimately be affected,” Andrew Tsai, an analyst with Jefferies, wrote in a research note. “We wonder if SRPT’s decision to suspend shipments is in part driven by some initial feedback from Elevidys’ certified care centers.”
Hospital suspends dosing
Tsai cited one example: Hours before Sarepta announced the pause, Children’s Hospital Los Angeles announced it would suspend all dosing of Elevidys.
“Our docs have previously said their use of Elevidys would be driven more by family choice (instead of their own), but perhaps docs could be more wary now,” Tsai added.
As with the two Elevidys patients, the LGMD patient who died succumbed to acute liver failure (ALF) after treatment with SRP-9004, a recombinant, adeno–associated viral vector (AAV) gene therapy. SRP-9004 is designed to deliver a full-length alpha-sarcoglycan transgene SGCA using the AAVrh74 vector, which, according to Sarepta, is designed to be systemically and robustly delivered to skeletal, diaphragm, and cardiac muscle.
Sarepta did not disclose the LGMD patient death on Wednesday when it announced it would “pause” development of SRP-9004 among most of the LGMD therapy candidates in its pipeline. “It was neither material nor central to the topics at hand on Wednesday,” Ingram told analysts Friday on a conference call, adding: “This wasn’t salient to our discussions.”
Ingram’s answer was challenged by Brian P. Skorney, a senior research analyst covering biotechnology for Baird: “It seems very clearly that this was a material event.”
Sarepta also said at the time it still planned to submit a Biologics License Application in the second half of this year for its furthest-along LGMD candidate SRP-9003, a gene therapy designed to treat LGMD type 2E/R4.
Also on Wednesday after the close of the markets, Sarepta announced a restructuring that will eliminate 36% of its workforce—approximately 500 jobs. Shares surged 19.5% the following day, in part because investors were relieved that the FDA did not withdraw Elevidys from the market, instead requesting the black box warning.
“We are charting unprecedented territory, making the story challenging to handicap,” Tsai cautioned investors. “Upcoming FDA discussions could be unfavorable for SRPT.”
The post About Face: Sarepta to Pause Elevidys Shipments Temporarily appeared first on GEN – Genetic Engineering and Biotechnology News.
