Stem Cell Treatment Responses Fails to Reach Statistical Significance and Has High Placebo Response Rate

In a phase 3 clinical trial (NCT03280056) of autologous neurotrophic factor-secreting mesenchymal stem cells (MSC-NTF)(NurOwn; BrainStorm Cell Therapeutics, New York, NY), 34.7% of participants with amyotrophic lateral sclerosis (ALS) and 27.7 % of those treated with placebo 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.

In the phase 3 clinical trial, responder analysis evaluating the proportion of participants who experienced a 1.25 points per month improvement in the post-treatment ALSFRS-R slope, was powered on assumed treatment response rates of 35% on MSC-NTF vs 15% on placebo. These estimates were based on available historical clinical trial data and the MSC-NTF phase 2 data. The trial met the expected 35% MSC-NTF treatment group efficacy response assumption, however the high placebo response exceeded placebo responses observed in contemporary ALS trials. The trial also measured average change in ALSFRS-R total score from baseline to Week 28, which was -5.52 with MSC-NTF vs -5.88 with placebo, a difference of 0.36 (P= .693).

"The consistency of effect observed across NurOwn treated patients, including within pre-specified subgroups, highlights an important treatment effect in a fatal disease with very limited treatment options. The placebo response observed in this trial is unprecedented and the ability to show treatment benefit in this context provides evidence of the clinical value of NurOwn. The robust changes in biomarkers of neurodegeneration. . .  . . . is encouraging", said Stacy Lindborg PhD, EVP and Head of Global Clinical Research. "More detailed analyses will be shared at upcoming scientific conferences and in subsequent publications.  We are committed to learning as much as we can from this trial and to partner with the ALS community to progress our collective understanding of ALS, which in turn will help us to continue to bring forward new treatments for this unrelenting disease." 

The phase 3 MSC-NTF trial was a multi-center, placebo-controlled, randomized, double-blind trial designed to evaluate the safety and efficacy of MSC-NTF in 189 participants with ALS. Potential participants with ALS 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 randomly assigned 1:1 to receive 3 intrathecal injections (8 weeks between each injection) of MSC-NTF or placebo. Participants were followed for 28 weeks after treatment. The primary endpoints of the trial were safety assessments and a responder analysis of the rate of decline in ALSFRS-R score over 28 weeks, where response was defined as participants with a 1.25 points/month improvement in the post-treatment versus pre-treatment slope in ALSFRS-R at 28 weeks following the first treatment.