The company will meet with the FDA again to discuss the future of the investigational cell therapy.
BrainStorm Cell Therapeutics has withdrawn its biologics license application (BLA) for debamestrocel (NurOwn), an investigational autologous mesenchymal stem cell (MSC) neurotrophic factor–secreting cell therapy product intended to treat amyotrophic lateral sclerosis (ALS), prior to its Prescription Drug User Fee Act action date, which was slated for December 8, 2023.1,2
BrainStorm pointed out that the withdrawal was made in coordination with the FDA and is perceived by the agency without prejudice. The company also stated that it intends to conduct a new registrational phase 3b clinical trial for NurOwn, which it now views as a necessary step on the course to any potential FDA approval for the cell therapy in ALS. Furthermore, BrainStorm noted that the FDA has invited it to a face-to-face meeting to discuss the future development plans and roadway to regulatory progress for NurOwn.
"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," Chaim Lebovits, the president and chief executive officer of BrainStorm, said in a statement.1 "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."
BrainStorm originally filed the BLA for the cell therapy 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 phase 3 clinical trial (NCT03280056) that evaluated the treatment in patients with ALS.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
The move to withdraw the BLA comes just a few weeks after an FDA Cellular, Tissue, and Gene Therapies Advisory Committee (AdComm) held to discuss the available data overwhelmingly voted negatively to the question: “Do the data presented demonstrate substantial evidence of effectiveness for treatment of mild to moderate ALS?”2 All told, 17 committee members of the AdComm voted no, 1 member voted yes, and 1 member abstained during the vote, which was held on September 27, 2023. At the AdComm, BrainStorm’s argument in favor of approval of the BLA largely focused on the potential impact of the floor effect on the results of the pivotal phase 3 clinical trial (NCT03280056) that evaluated the treatment against a placebo in patients with ALS, which did not meet any of its primary or key secondary end points.
“It's possible that this therapy has some benefit for some patients,” AdComm committee member Lynn A. Raymond, MD, PhD, the director of the Djavad Mowafaghian Centre for Brain Health, said after voting no.2 “But we look at the total when we have to decide whether this goes forward to public market and there wasn't evidence for the whole group that this was effective and there was evidence to potentially suggest it was actually deleterious at least for those who are maybe more advanced with ALS, causing more deaths and causing more bulbar dysfunction. So for that reason, I vote no...”