Final Operational Milestone #7
The Phase 3 clinical trial clinical data was published in the peer-reviewed journal Muscle and Nerve in December 2021. The paper, entitled “A Randomized Placebo-Controlled Phase 3 Study of Mesenchymal Stem Cells Induced to Secrete High Levels of Neurotrophic Factors in Amyotrophic Lateral Sclerosis,” shows that although the trial did not reach statistical significance on the primary or secondary endpoints, pre-specified and post hoc analyses show a NurOwn-induced treatment effect across both primary and secondary efficacy outcomes in those with less advanced disease.
An erratum (‘correction’) to the phase 3 NurOwn clinical trial publication was published in Muscle & Nerve in August 2022. The corrected analyses strengthened previously communicated conclusions ; despite not meeting statistical significance in the primary and key secondary outcomes in the total study population, the phase 3 study demonstrated clinically meaningful and statistically significant preservation of ALS function (ALSFRS-R responder analysis and change from baseline) in NurOwn compared to placebo treated participants in the prespecified subgroup with less advanced disease (ALSFRS-R 35 or greater at baseline). Detailed post-hoc analyses that corrected for the ALSFRS-R floor effect (inability of the ALSFRS-R scale to accurately measure progression in more advanced study participants with ALSFRS-R scores at or below 25 at baseline) confirmed the observed treatment benefit. Further analyses demonstrating consistent cerebrospinal fluid biomarker treatment effects above or below the ALSFRS-R threshold of 25, confirmed consistent biological effects of NurOwn treatment vs. Placebo across ALS disease pathways, independent of the observed ALSFRS-R scale limitations in more advanced ALS study participants.
Phase 3 study results were presented at several scientific venues including:
A presentation titled “NurOwn® Phase 3 ALS Clinical Trial Update” at the Virtual 12th Annual California ALS Research Summit
The presentation titled “Relationship UNC13A Single-Nucleotide Polymorphisms to Clinical Outcomes in NurOwn® Phase 3 ALS Clinical Trial” allele presented at the 2022 Muscular Dystrophy and Association Clinical and Scientific Conference focused on pre-specified genetic analyses from the NurOwn® Phase 3 trial in ALS which suggests that NurOwn® treatment may influence disease progression in patients who possess the UNC13A risk allele.
A scientific abstract titled “CSF Biomarkers Evaluated by Principal Component Analysis in a NurOwn® Phase 3 Clinical Trial” presented at the AAN 2022 Virtual Congress
A presentation titled “Advancing novel CSF biomarkers to evaluate ALS target engagement & improve therapeutic outcomes” delivered at the ALS Drug Development Summit, Boston MA
Insights into the ALS Phase 3 primary endpoint leveraging ENCALS model patient prognosis trajectories were presented as a scientific poster at the European Network to Cure ALS (ENCALS) meeting in Edinburgh, Scotland June 1-3, 2022.
New biomarker analyses from NurOwn’s Phase 3 ALS Trial were presented at the ALS ONE Research Symposium in a presentation titled “The Relationship between CSF Biomarkers and Efficacy of Treatment with NurOwn (MSC-NTF cells).”
A scientific poster titled “Further Analysis of NurOwn Phase 3 Data Based on Baseline ALSFRS-R Status Clarifies Treatment Outcomes” was presented at the 2022 NEALS Meeting, held November 1-3, 2022 in Clearwater Beach, Florida. The presentation titled, “The Relationship between CSF Biomarkers and Efficacy of Treatment with NurOwn (MSC-NTF cells)” summarized new post hoc analyses that account for ALSFRS-R floor effects and add to the robust body of evidence supporting a clinically meaningful treatment effect with NurOwn in ALS.