Brainstorm Cell Therapeutics reported topline results from a Phase 3 trial evaluating NurOwn (MSC-NTF cells) as a treatment for Amyotrophic lateral sclerosis (ALS). Although the data showed a numerical improvement in the treated group compared to placebo across the primary and key secondary efficacy endpoints, the trial did not reach statistically significant results. However, NurOwn did result in a clinically meaningful treatment response compared to placebo in a pre-specified subgroup of patients with early disease. NurOwn treatment also led to significant increases in neurotrophic factors as well as a reduction in both neuroinflammatory and neurodegenerative biomarkers.
The multi-center, placebo-controlled, randomized, double-blind trial was designed to evaluate the safety and efficacy of NurOwn in 189 ALS patients. It was conducted at six medical centers: University of California Irvine (Dr. Namita Goyal); Cedars-Sinai Medical Center (Dr. Matthew Burford); California Pacific Medical Center (Prof. Robert Miller); Massachusetts General Hospital (Prof. Merit Cudkowicz, Dr. James Berry); University of Massachusetts Medical School (Prof. Robert Brown) and Mayo Clinic (Prof. Anthony Windebank, Dr. Nathan Staff). ALS patients were screened during an 18-week run-in period and those who were rapid progressors (defined as patients with at least a 3 point decrease in ALSFRS-R score during the run-in period) were randomized 1:1 to receive three intrathecal injections (8 weeks between each injection) of NurOwn or placebo. Patients were followed for 28 weeks after treatment.
During a follow-up period of 28 weeks, the investigators assessed safety as well as the rate of decline in the ALSFRS-R score. Participants who had a 1.25-points/month improvement in the post-treatment ALSFRS-R slope were considered to have met the primary endpoint. Additional secondary endpoints were the percentage of patients with halted disease progression, combined analysis of function and survival, slow vital capacity, tracheostomy-free survival and overall survival, among others.
The clinical trial did show a clinically meaningful treatment response across the primary and key secondary endpoints in a pre-specified subgroup of patients with early disease. Approximately 34.6% of responders in this subgroup met the primary endpoint definition on NurOwn versus 15.6% of patients who received placebo, but again the differences were not statistically significant. The mean change from baseline to week 28 in the ALSFRS-R total score was -1.77 and -3.78 with NurOwn and placebo, respectively. The investigators noted this represented an improvement of 2.01 ALSFRS-R points, ultimately favoring NurOwn.
“This clinical trial included a more severely affected ALS population compared to other recent ALS clinical trials. We identified a superior treatment response in a pre-specified subgroup of patients with less advanced disease. We are in active discussions with the FDA who have expressed their eagerness to review the data and have committed to prioritize review of this data. The FDA will review the data to see if there is a path forward to support approval” said Chaim Lebovits, Chief Executive Officer of BrainStorm.
The NurOwn technology platform (autologous MSC-NTF cells) represents a promising investigational 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 can 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.
Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, is a progressive disease that causes damage to cells in the brain and spinal cord known as motor neurons. Motor neurons transmit signals from the brain to the muscles. When motor neurons become damaged and eventually die, the brain can no longer control muscle actions. The motor neurons affected in ALS are those that initiate and control voluntary movements. With the progressive loss of voluntary muscle action, patients with ALS may lose their ability to speak, eat, move and breathe.