A group of advisers to the Food and Drug Administration on Wednesday determined that a controversial therapy for ALS does not have enough evidence to merit approval.
In an 17-1 vote, the expert panel agreed with agency scientists that the drug, developed by BrainStorm Cell Therapeutics, doesn’t appear effective for ALS, or amyotrophic lateral sclerosis. One committee member abstained.
“I wanted to be able to approve this, but in the end I just did not see the data there,” Jan Nolta, director of the stem cell program at the University of California Davis Health and a committee member, said after the vote.
The vote came after FDA staff laid out a litany of concerns with BrainStorm’s results and the company’s ability to safely produce the therapy, which consists of a patient’s own stem cells. Reviewers also rejected after-the-fact analyses done by BrainStorm that the company said showed signs its therapy worked in certain patients.
“The totality of data submitted in this [application] does not demonstrate substantial evidence of effectiveness of [the therapy] for the treatment of ALS or a subgroup of ALS,” said Gumei Liu, the FDA’s clinical reviewer, in a meeting presentation. “New adequate and well-controlled clinical studies would be needed.”
The FDA isn’t required to follow the advice of its advisory committees, although it usually does. The regulator has set a date of Dec. 8 to decide on approval.
Called NurOwn, the therapy has taken an unorthodox path to reach this point. A Phase 3 study testing the treatment in about 200 people with ALS failed to meet any of its goals in late 2020, and showed worse survival for participants on the drug.
But BrainStorm submitted for approval last year anyway, citing those after-the-fact, or “post hoc” analyses. In November, the FDA turned back the company’s application, which it determined to be “scientifically incomplete” and reliant on “grossly deficient” data, according to documents published Monday. BrainStorm then took the rare step of filing its application over the FDA’s protest, leading to Wednesday’s meeting.
Over that time, NurOwn, and BrainStorm’s attempt to secure its approval, has become a divisive topic — a flash point in a broader debate over how flexible the FDA should be in reviewing new ALS medicines. The agency recently approved two new drugs for the disease despite mixed data, a fact BrainStorm cited.
The ALS patient community argues that the severity of the disease, which inexorably erodes muscle function and typically leads to death in a few years’ time, requires more pliant regulatory standards. And in the case of NurOwn, ALS patients and their caregivers point to powerful anecdotal reports of improvement from treatment.
Nearly a dozen ALS patients and their family members testified at Wednesday’s meeting in support of NurOwn. They spoke of their experience, or that of their loved ones’, in BrainStorm’s trial or subsequent “expanded access” study, describing new strength, clearer speech or easier breathing.
“After treatment … I was able to do certain things with my hands that I had lost the ability to do,” said Philip Green, a 53-year-old man with ALS, at the meeting. “I could once again pick up my phone and the TV remote, and use them without dropping them.”
Patients argued that even small benefits mattered to them, and that they would be willing to tolerate the drug’s side effects and onerous delivery for that chance.
“There is no risk worse than a certain death from a 100% fatal condition,” said Ajay Sampat, a neurologist at UC Davis who has ALS.
Advisers weighed patients’ testimony against the negative trial data and the FDA’s many criticisms of Brainstorm’s application.
“[The clinical data] are just disappointing, and they’re hard to reconcile with the compelling anecdotal evidence of effectiveness that we heard from the public speakers,” said G. Caleb Alexander, a professor of epidemiology and medicine at Johns Hopkins University and a committee member.
The panel also questioned BrainStorm’s explanation of how its treatment is meant to work, and were troubled by the manufacturing issues that the FDA raised. Tabassum Ahsan, the committee’s chair and vice president of cell therapy operations at City of Hope, described the meeting as a “missed opportunity” for BrainStorm to address those issues.
“We firmly believe in the totality of our data,” said BrainStorm’s co-CEO Stacy Lindborg, in an interview after the vote. “Had more time and opportunity been allowed, many of the questions that were being discussed …we could have sufficiently addressed.”
Advisers additionally discussed how a follow-up study could better test NurOwn and validate the post-hoc analyses BrainStorm presented. The company presented plans Wednesday for another placebo-controlled trial that would run, over three phases, for about two years.
But BrainStorm may be hard-pressed to complete such a trial. The company reported it held only about $750,000 in cash, cash equivalents and short term deposits at the end of June.
“In the upcoming weeks, we will explore all the options available to us to proceed with a product that we firmly believe in,” said Lindborg.