Gene therapy deaths push back Astellas-Audentes' approval by at least two years
The three deaths in an Astellas gene therapy trial last year will push back the experimental therapy’s approval by “more than two years” as Astellas plans a second study, the company told Endpoints News in an email Tuesday. That means a regulatory application would not come until at least mid-2022.
When Astellas bought out the gene therapy biotech Audentes for $3 billion in December 2019, the Japanese pharma believed they could file for approval for their lead candidate in the US in mid-2020 and in Europe in the latter half of 2020. The therapy was a one-time treatment for a rare and deadly muscle-wasting disorder X-linked myotubular myopathy, or XLMTM, and executives believed the 26-person study would be enough to secure approval.
But in May, the first of what would ultimately be three patient deaths occurred after suffering a severe reaction to a high dose of the vector. The study was halted while investigators tried to determine what happened.
Although the FDA agreed to allow Astellas to resume the study at a lower dose last December, they have yet to enroll new patients. The company said in the Tuesday email that they planned to do so by June. The path to approval, however, remains uncertain.
“We can’t provide an accurate timeline at this stage,” a spokesperson said. “But filing with the FDA and EMA is expected to be delayed more than two years.”
The plan for submission, they said, had changed. Originally, Astellas planned on submitting the therapy for approval for patients of all ages after completing the first trial, known as ASPIRO, even though ASPIRO only enrolled patients up to the age of five.
Now, however, they believe they need to finish the ASPIRO trial and then run a second study for patients over the age of 5. The three boys who died — almost all XLMTM patients are male — were among the oldest and largest patients in the initial trial, meaning they received among the highest doses and raised concerns about how to bring the therapy to older patients.
Astellas is waiting to complete dosing in ASPIRO before planning the second trial, the spokesperson said, “so that additional clinical data can best inform the approach.” The company plans to meet with the FDA this spring and the EMA this summer to prepare for a filing.
Earlier this week, Astellas announced that it had written off $540 million of the $3 billion buyout, citing their belief that the drug would be approved later and for a smaller patient population than originally thought.
Despite the tragic setbacks, investigators say the therapy remains a promising treatment for a genetic disease that kills most patients before they reach adulthood. Kids who received a low dose of the therapy hit key motor milestones for the first time: Six out of six were able to breathe without a ventilator and five out of six were able to walk for the first time.
Still, Astellas has drawn criticism from outside experts and executives for failing to disclose or publish detailed information around the patients’ deaths, leaving open the question of precisely what went wrong and how to prevent it in the future.