NurOwn® Phase 2 ALS Trial: ALSFRS-R Improvement is Reflected in Subscale Domains (S38.002)

Objective: To evaluate the contribution of the four ALSFRS-R domains to the overall ALSFRS-R efficacy outcome in the NurOwn ® U.S, Phase 2 ALS multicenter double-blind placebo-controlled trial (NCT02017912). Background: MSC-NTF cells (NurOwn ® ) are autologous bone-marrow derived mesenchymal stem cells (MSC) induced to secrete high levels of neurotrophic factors (NTFs). MSC-NTF cells were evaluated for safety and efficacy. Design/Methods: 48 ALS participants were randomized 3:1 (active: placebo) and followed for 6-months post-transplantation. Responder analyses compared the treated to placebo groups in the following outcomes: ≥1.5 points/month improvement in ALSFRS-R total score; and ≥0.375 points/month (25% of 1.5) improvements in each of the four subscales measuring the bulbar, gross motor, breathing, and fine motor domains. Results: The trial met its primary safety endpoint. A higher percentage of study participants achieved ≥1.5 points/month improvement in the treated group at all time points, was significantly higher in the treated group at 4-weeks (one-sided, p=0.02) and 12-weeks (one-sided, p=0.08), and was more evident in the subgroup that excluded slow progressors (pre-treatment change ALSFRS-R ≥ −2). The percentage of responders (≥0.375 points/month improvement) in the ALSFRS-R bulbar domain (excluding slow progressors) was significantly higher in the treated group at 4-weeks (47% vs 0, one-sided, p=0.08), 8-weeks (47% vs 0, p=0.08), 12-week (40% vs 0, p=0.09), 16-weeks (47% vs 0, one-sided, p=0.06), and 24-weeks (40% vs 0, one-sided, p=0.09). The percentage of responders (≥0.375 points/month improvement) in the ALSFRS-R fine motor domain (excluding slow progressors) was significantly higher in the treated group at 2-weeks (87% vs 40%, one-sided, p=0.07). A higher number of participants in the treated group demonstrated ≥0.375 points/month improvement in gross motor and breathing domains, although these did not reach statistical significance. Conclusions: The observed improvements following MSC-NTF transplantation are reflected in all four ALSFRS-R domains, particularly in the bulbar and fine motor subscales. Disclosure: Dr. Kern has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Brainstorm Cell Therapeutics Ltd. Dr. Cudkowicz has nothing to disclose. Dr. Berry has nothing to disclose. Dr. Windebank has nothing to disclose. Dr. Staff has nothing to disclose. Dr. Owegi has nothing to disclose. Dr. Lebovits has nothing to disclose. Dr. Gothelf has nothing to disclose. Dr. Brown has nothing to disclose.