BrainStorm Cell Therapeutics issued a statement Tuesday supporting a Citizens’ Petition submitted to the FDA requesting the approval of its cell therapy NurOwn, whose BLA was withdrawn in 2023. A Phase IIIb trial was scheduled to begin last month.
The story of BrainStorm Cell Therapeutics’ NurOwn has a new chapter. Last week, several people with amyotrophic lateral sclerosis submitted a Citizens’ Petition to the FDA requesting that the agency approve the stem cell therapy based on “new evidence and totality of evidence.”
Tuesday, BrainStorm acknowledged the Citizens’ Petition and said that seeking a new review of NurOwn’s data “will provide a critical opportunity to reaffirm its potential as therapy for amyotrophic lateral sclerosis (ALS).”
The Tel Aviv and New York–based company has been through the regulatory wringer during the past five years with NurOwn. In 2021, the FDA advised BrainStorm that its Phase III trial—which did not meet the primary endpoint—was insufficient to support a Biologics License Application (BLA).
The following year, BrainStorm was rebuffed again when the FDA issued a Refusal to File Letter for a BLA the company had submitted based on a correction to analyses of the Phase III trial—a change it claimed resulted in a statistically significant treatment difference. The persistent biotech then sought and secured an advisory committee meeting for NurOwn, but this resulted in a 17-1 vote against the therapy and the company’s withdrawal of the BLA prior to its Dec. 8, 2023 PDUFA date.
The company instead decided to push forward with a Phase IIIb trial, which had an estimated start date of June 30, according to clinicaltrials.gov. In an email Tuesday afternoon, a BrainStorm representative told BioSpace the trial will commence upon securing funding. Fifteen clinical trial sites have been selected and Clinical Trial Agreements are currently being executed, they said.
Despite mutually agreeing with the FDA on the path forward with the Phase IIIb trial, BrainStorm has long contended that the missed endpoint in the first Phase III trial was due to a “floor effect,” which occurs when the scale of measurement is unable to capture patients’ progression as their condition becomes severe.
That trial’s primary endpoint— a 1.25 points per month improvement on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R)—was met by 34.7% of NurOwn participants versus 27.7% of placebo comparators. However, in a pre-specified subgroup of patients with early-stage disease, the difference was much larger, at 34.6% vs. 15.6%.
Additionally, recently reported data from 10 Phase III participants who entered NurOwn’s expanded access program (EAP) after the trial showed that nine survived more than five years from ALS symptom onset, according to a press release issue by BrainStorm on June 16. According to other published estimates, approximately 10% of people with ALS survive past 5 years, BrainStorm said. Median survival in the EAP was 6.8 years from symptom onset.
“These results strongly suggest that the observed survival outcomes in the EAP patients are unlikely to be due to chance alone and further underscore the need for continued scientific exploration,” BrainStorm said in Tuesday’s release.
In an email to BioSpace, a representative for the patient petitioners pointed to Phase III and EAP data including “100% five-year survival versus 20% ALS natural history” and “extended periods of progression-free survival (PFS) ranging from a few months up to 17 months when receiving NurOwn.” These data, they said, document changes that are “unprecedented in the history of ALS clinical trials.”
The Citizen Petition for NurOwn comes on the heels of a difficult phase for the ALS community. After winning approval as just the third-ever drug for ALS in September 2022, Amylyx withdrew Relyvrio from the U.S. and Canadian markets last spring after it failed its highly anticipated Phase III PHOENIX trial. Research is ramping up again, however, with companies like Korro Bio, Coya Therapeutics and QurAlis all exploring novel targets against the devastating neurodegenerative disease.
Editor’s note (July 8): This story has been updated from its original version to include further details from BrainStorm on the Phase IIIb trial of NurOwn.
