BRAINSTORM CELL THERAPEUTICS PHASE II TRIAL RESULTS
July 18, 2016
Hope NOW For ALS is honored to be participating with Brainstorm and its statisticians and investigators in the analysis of their U.S. phase 2A clinical trial of NurOwn. Today Brainstorm announced the results of that trial. First, and most importantly, the trial demonstrated safety beyond any doubt. The trial was a randomized double-blind placebo group trial conducted at three centers: Massachusetts General Hospital, University of Massachusetts Medical Center and the Mayo Clinic. Two-thirds of the patients received the treatment and one-third a placebo. Initially 48 patients were enrolled; three dropped out at mid-trial. While the trial was not sufficiently powered to attain the FDA’s traditional definition of efficacy (a P value < 0.05 comparing mean progression of the treated group to the placebo group), an in-depth analysis of the data indicates significant and positive results.
First, looking at the “responders” (ALSFRS score progression rate pre-treatment (3 months) is slowed by 100% or more after treatment), there was a clear, disproportionate favorable impact in the treatment group at 2 and 4 weeks. A few positive responses in the placebo group indicate the presence of a “placebo effect” (when patients receiving a placebo feel they are improving). However, by week 12 the placebo effect all but disappeared. The responders (40% of the treated group) however, still showed positive responses at week 12. The degree of positive response was noticeably diminished by week 24. Significantly, if a “responder” is defined as one whose ALSFRS score slope improves by 1.5 points per month, at 4 weeks post treatment nearly half of the treated group met the definition of “responder”, and only one in the placebo group. At 12 weeks, approximately 25% of the treated group still met the definition of “responder” and no one in the placebo group. Clearly the treatment produced a beneficial impact for a significant percentage of the trial participants.
When slow progressors are excluded from the data analysis, benefits are easier to detect and the results appear even more favorable. (Unfortunately, the power of this subset analysis is probably insufficient to persuade the FDA to grant approval). In addition, as Dr. Merit Cudkowicz observed, after 2 weeks the treated group showed increased levels of growth factors and decreased inflammatory markers in their cerebrospinal fluid (”CSF”) – strong evidence of a biological effect. When coupled with the responder analysis, it underscores the positive results.
The timing of the observed improvements was relatively consistent with the science concerning stem cell therapy; repeated applications are suggested to be most effective due to the relatively short half-life of stem cells once introduced into the body.
Hope NOW For ALS performed an additional analysis looking at demographic patterns in the trial population as possible predictors of responses. We found a relatively high correlation in responders to: 1) age, and 2) baseline SVC level. The majority of the responders were under age 51 with an SVC ≥ 80% at the start of the trial. Responders older than 51 all had an SVC ≥100% at the start of the trial. This observation produces the algorithm below to predict responders and non-responders:
Likely responders: Age of patient ÷ (0.1 × SVC) < 7.0
Brainstorm and clinical trial investigators have indicated a desire to conduct a higher powered Phase 3 trial. While we support this, we also know that raising the necessary funding from investors for a Phase 3 trial could be a very lengthy process, possibly years. Hope NOW For ALS believes the evidence of efficacy in the Phase 2 trial warrants applying for an Accelerated Approval (AAP), subject to a Phase 4 confirmatory trial. Discussions with the FDA should begin immediately. We are eager to assist Brainstorm and the investigators to bring this extremely promising treatment to the clinic as soon as possible. We join Brainstorm in thanking the patients who participated in this trial – you are making a significant contribution to the pursuit of a cure.
Hope NOW for ALS
Board of Directors:
Bob Hebron (ALS caregiver, NJ)
Jehad Majed (ALS caregiver, MI)
Linda Clark (widowed ALS caregiver, CA)
Eric Valor (person with ALS, CA)
Dr. Stephen Finger (person with ALS, SC)
Jay Smith (person with ALS, TX)