Phase III trial of NurOwn shows evidence of mechanism of action in amyotrophic lateral sclerosis.- BrainStorm Cell Therapeutics
BrainStorm Cell Therapeutics announced the presentation of new biomarker analyses supporting the therapeutic benefit of NurOwn in amyotrophic lateral sclerosis (ALS) at the ongoing 5th Annual ALS ONE Research Symposium.
The presentation was delivered by Dr. Stacy Lindborg, Chief Development Officer at Brainstorm, and entitled, "The Relationship between CSF Biomarkers and Efficacy of Treatment with NurOwn (MSC-NTF cells)."
NurOwn's Phase III trial is a strong outlier compared to other late-stage ALS trials due to the inclusion of participants with more advanced disease. The average ALSFRS-R score in NurOwn's Phase III trial was 31, 5 points lower than the registrational trial for the most recently FDA-approved therapy. The inclusion of more advanced participants impacts the assessment of all clinical endpoints based on the ALSFRS-R, as a result of the inability to measure ongoing clinical decline with scale in these participants (i.e., a floor effect). To draw valid conclusions from clinical endpoint data collected in the trial, the floor effect must be addressed. As previously announced, a NurOwn treatment effect was observed in participants in a pre-specified subgroup with less advanced disease (ALSFRS-R baseline score of at least 35) across two endpoints: the primary endpoint (clinical responder analysis) and a key secondary endpoint (average change from baseline to the end of the trial). The difference between NurOwn and placebo for this key secondary endpoint was nominally statistically significant (p=0.050).
An analysis was performed to evaluate the effects of NurOwn and placebo on cerebrospinal fluid (CSF) biomarkers across pathways important to ALS of neuroinflammation, neurodegeneration and neuroprotection. Additional goals were to understand the role that baseline ALSFRS-R values plays on biomarker trajectories and to understand the predictive power of biomarkers on clinical outcomes. As observed in earlier trials, NurOwn was shown to decrease biomarkers associated with neuroinflammation and neurodegeneration, and increase neuroprotective biomarkers over 20 weeks, demonstrating its multifaceted mechanism of action. New analyses looked at the trajectory of biomarkers for the subgroups of participants with baseline ALSFRS-R scores >25 and less than or equal to 25, those most likely to be impacted by the floor effect of the scale. Decreases in neuroinflammatory and neurodegenerative markers and increases in neuroprotective markers in NurOwn treated participants compared to placebo were observed in both subgroups. These results indicate that NurOwn had similar biological effects on ALS participants regardless of the level of disease progression at baseline. Further statistical modeling pre-specified prior to unblinding of the data identified three biomarkers that were predictive of clinical outcomes: baseline LAP, baseline neurofilament light (NfL) and mean change in Galectin-1. These biomarkers relate to neuroinflammatory, neurodegenerative, and neuroprotective pathways, respectively.
