The company characterized the meeting as “productive”.
BrainStorm Cell Therapeutics has met with the FDA to discuss a possible regulatory path forward for debamestrocel (NurOwn), its investigational autologous mesenchymal stem cell (MSC) neurotrophic factor–secreting cell therapy product intended to treat amyotrophic lateral sclerosis (ALS).1
Following the meeting, which the company characterized as “productive”, BrainStorm noted that it is now seeking a Special Protocol Assessment (SPA) from the agency for a planned registrational phase 3b clinical trial. As part of the process, which the company intends to use to come into alignment with the FDA on critical elements of the study design, such as patient eligibility, end points, and planned analyses, BrainStorm plans to provide the agency with documentation supporting the SPA.
"Our meeting with the FDA provided us with valuable input on the phase 3b trial design, outlining clear steps forward," Chaim Lebovits, the president and chief executive officer of BrainStorm, said in a statement.1 "We believe that a SPA will serve to help derisk certain regulatory aspects of the NurOwn clinical program. We recognize the urgency in providing ALS patients with safe and efficacious treatments and are committed to agreeing on a regulatory path forward for NurOwn. We are grateful for the FDA's continued support and guidance and look forward to providing further updates once we have more clarity on an SPA."
The planned phase 3b clinical trial would be BrainStorm’s second attempt at a registrational clinical trial for NurOwn. The cell therapy was previously evaluated in a pivotal phase 3 clinical trial (NCT03280056) that tested the treatment against a placebo in patients with ALS, but did not meet any of its primary or key secondary end points. Despite the setbacks, BrainStorm still sought to make a case for NurOwn based on the trial data with posthoc sensitivity analyses intended to account for the floor effect, a phenomena resulting from the fact that the ALS Functional Rating Scale used in the study cannot measure disease progression after a certain point in patients with advanced ALS.2
BrainStorm originally filed a biologics license application (BLA) for NurOwn in September 2022, in spite of FDA feedback received in February 2021 that recommended against filing based on a summary of high-level data from the pivotal trial.3,4 After several interactions with the agency, the company requested use of the FDA's "File Over Protest" procedure to move the regulatory process forward and as a result, on February 7, 2023, the FDA continued its review of the BLA.3
More recently, on September 27, 2023, an FDA Cellular, Tissue, and Gene Therapies Advisory Committee (AdComm) was held to discuss data from the pivotal trial and the question “Do the data presented demonstrate substantial evidence of effectiveness for treatment of mild to moderate ALS?” The committee overwhelmingly voted negatively, with 17 members voting no, 1 member voting yes, and 1 member abstaining.
Following the AdComm, BrainStorm announced on October 18, 2023, that it had pulled its BLA for NurOwn ahead of its Prescription Drug User Fee Act action date, which was slated for December 8, 2023.2,5 BrainStorm indicated that the withdrawal was made in coordination with the FDA and was perceived by the agency without prejudice.
"We are confident in the data supporting the value of NurOwn as an addition to the options for treating ALS, and we have every desire to bring it to the ALS community," Lebovits said in a statement at the time.5 "We look forward to working with the FDA to define the path forward. We understand that an additional pivotal trial will be necessary, and we are doing everything in our power to execute on this as quickly as possible."