FDA Issues Refusal To File Letter for New Biologics License Application for Stem Cell ALS Treatment

The Food and Drug Administration (FDA) has issued a refusal to file letter for the Biologics License Application (BLA) for autologous neurotrophic factor-secreting mesenchymal stem cells (MSC-NTF)(NurOwn; BrainStorm Cell Therapeutics, New York, NY) as treatment of amyotrophic lateral sclerosis (ALS). The company may request a Type A meeting to discuss the content of the refusal to file letter per the FDA. 

"While we are disappointed that the FDA has not accepted our BLA for NurOwn in ALS, we remain committed to NurOwn's advancement as a treatment for this devastating disease. The company intends to request a Type A meeting and looks forward to continued discussions with the FDA," said Chaim Lebovits, chief executive officer of BrainStorm. "We continue to believe that NurOwn's phase 3 trial represents a significant contribution to ALS therapy and will continue to work tirelessly to address the needs of people living with ALS by advancing science and partnering with researchers around the world."

In the phase 3 clinical trial (NCT03280056), participants with ALS (n=189) treated with placebo or MSC-NTF had a 1.25 point reduction in disease progression (P=.453). Disease progression was measured by the rate of change in scores on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). The difference between stem-cell treatment and placebo did not reach statistical significance because of the high response rate seen with placebo.

Dr. Robert Brown, director of the Program in Neurotherapeutics at the University of Massachusetts Medical School, Dr. Merit Cudkowicz, chief of Neurology at Massachusetts General Hospital, Julieanne Dorn professor of Neurology at Harvard Medical School, director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital jointly stated, "While the prespecified primary outcome measure was not met, there were participants with beneficial clinical effects and overall changes in relevant biomarkers of drug effect. Understanding whether there are people with ALS who might respond better to NurOwn is important given the unmet therapeutic need. As the 3 coPIs of the phase 3 study of NurOwn, we support continued discussions with the FDA on the best path forward."