BrainStorm Cell Receives FDA Refusal to File Letter for its New BLA for NurOwn for the treatment of ALS

Rare Daily Staff

BrainStorm Cell Therapeutics, a developer of cellular therapies for neurodegenerative diseases, said the company has received a refusal to file letter from the U.S. Food and Drug Administration regarding the company’s new Biologics License Application for NurOwn for the treatment of amyotophic lateral sclerosis (ALS).

The FDA did not say why it refused to file but indicated that the company can request a Type A meeting to discuss the content of the refusal to file letter.

“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, CEO 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.”

ALS is a progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death. More than 90 percent of people with ALS have sporadic disease, showing no clear family history. ALS affects approximately 29,000 people in the U.S.

Brainstorm Cell says its NurOwn technology platform (autologous MSC-NTF cells) represents a promising therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells are designed to effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression.

BrainStorm completed a phase 3 trial in 200 participants with ALS.  In the attempt to examine a real-world population, the study enrolled people with more advanced disease than other late-stage ALS trials. In fact, more than a third of these participants with advanced disease entered the trial with the one or more dimensions of physical function (e.g., dressing/hygiene, cutting food, walking) starting at the lowest possible score of 0 on the ALSFRS-R; thereby preventing the measurement of further deterioration. A pre-specified subgroup of participants, with baseline ALSFRS-R³35, which controls for this “scale effect” showed a trend to a meaningful increase in the clinical response with NurOwn compared to placebo. The secondary endpoint, average ALSFRS-R change from baseline to 28 weeks in this subgroup, was statistically significant (p=0.050, Muscle and Nerve Supplemental File and Muscle and Nerve Erratum). In addition, post-hoc sensitivity analyses were presented one week ago at the 21st Annual NEALS Meeting 2022, which also showed a statistical trend towards a clinically meaningful treatment effect with NurOwn across subgroups, and one that is consistent with the pre-specified subgroup of participants with less advanced ALS at baseline.  Finally, biomarker data in all trial participants also showed consistent patterns of NurOwn reducing markers of inflammation and neurodegeneration, and increasing neuroprotective and anti-inflammatory markers relative to placebo, further supporting the notion that trial participants taking NurOwn are indeed experiencing a positive biological effect.

The three co-principal investigators of the NurOwn phase 3 study, Robert Brown of the University of Massachusetts Medical School, Merit Cudkowicz at Massachusetts General Hospital, and Tony Windebank of the Mayo Clinic said in a statement: “While the pre-specified 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 three co-PIs of the phase 3 study of NurOwn, we support continued discussions with the FDA on the best path forward.”

Photo: Chaim Lebovits, CEO of BrainStorm Cell Therapeutics