BrainStorm ALS Therapy Fails to Meet Endpoints in Late-Stage Study

BrainStorm ALS Therapy Fails to Meet Endpoints in Late-Stage Study

Rare Daily Staff

BrainStorm Cell Therapeutics said topline results from its late-stage study of its adult stem cell therapy NurOwn as a treatment for amyotrophic lateral sclerosis failed to meet primary and key secondary endpoints compared to a placebo.

The study showed NurOwn was generally well tolerated in this population of rapidly progressing ALS patients. While the study did show a numerical improvement in the treated group compared to placebo, the trial did not reach statistically significant results.

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.

The NurOwn technology platform is an 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.

The phase 3 clinical trial’s primary efficacy endpoint, a responder analysis evaluating the proportion of participants who experienced a 1.25 point per month improvement in the post-treatment Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) slope, was powered on assumed treatment response rates of 35 percent on NurOwn versus 15 percent on Placebo. These estimates were based on available historical clinical trial data and the NurOwn phase 2 data.

The primary endpoint was achieved in 34.7 percent of NurOwn participants versus 27.7 percent for placebo. Therefore, the trial met the expected 35 percent NurOwn treatment group efficacy response assumption, however the high placebo response exceeded placebo responses observed in contemporary ALS trials. The secondary efficacy endpoint measuring average change in ALSFRS-R total score from baseline to Week 28 was -5.52 with NurOwn versus -5.88 on Placebo, a difference of 0.36.

The company said in a pre-specified subgroup with early disease based on ALSFRS-R baseline score 35, NurOwn demonstrated a clinically meaningful treatment response across the primary and key secondary endpoints and remained consistent with its pre-trial, data-derived assumptions. 

In this subgroup, there were 34.6 percent responders who met the primary endpoint definition on NurOwn and 15.6 percent on placebo, and the average change from baseline to week 28 in ALSFRS-R total score was -1.77 on NurOwn and -3.78 on placebo, an improvement of 2.01 ALSFRS-R points favoring NurOwn.

Cerebrospinal fluid (CSF) biomarker analyses confirmed that treatment with NurOwn resulted in a statistically significant increase of neurotrophic factors and reduction in neurodegenerative and neuroinflammatory biomarkers that was not observed in the placebo treatment group.

The study also carried out pre-specified statistical modeling designed to predict clinical response with high sensitivity and specificity based on ALS biomarkers and ALS Function and confirmed that NurOwn treatment outcomes could be predicted by baseline ALS function as well as key CSF neurodegenerative and neuroinflammatory biomarkers.

“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,” said Chaim Lebovits, CEO of BrainStorm. “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.”

Photo: Chaim Lebovits, CEO of BrainStorm