Neuralstem recently announced via press release results from a Phase 2 clinical trial of their fetal-derived stem cell treatment, NSI-566. According to their statement, only one person in the 15-person study failed to tolerate the surgical procedure involving the injection of up to 16 million stem cells directly into the spinal cord. The primary endpoint defined for the study was not safety. From early analysis of the data, the company reports that endpoint was met. An earlier clinical trial conducted in ALS patients also reported similar results regarding safety. Neuralstem also included early analysis on the effects of their stem cell treatment on the progression of ALS. According to their press release, nearly half of people in the trial responded to the treatment in a positive way. A positive response is defined by Neuralstem as a positive change in the rate of procession as measured by ALSFRS-R or a positive change in grip strength tests. No further details were provided about this cohort, which they term the responder group. The other half of the patients in the trial, termed the nonresponder group, saw a negative change in the rate of progression as measure by ALSFRS-R or a negative change in grip strength tests. Nowhere is the release did they describe an objective measure that could differentiate a responder from a nonresponder before enrolling a patient in the trial. That work is ongoing according to several of the investigators quoted in the company's press release.
While the trial was not intended to measure efficacy, the data in the press release seemed to suggest that Neuralstem wanted to communicate on that topic. There was no placebo arm in this study, and no attempt to compare the data to a standard of care or placebo arm was made in the press announcements. All patients were given some amount of modified stem cells which the company hoped would engraft into the spine, replacing cells lost to the disease and providing support to remaining motor neurons. However, specific dosing for each patient or across the proposed responder and nonresponder groups were not provided in the press release statement. That is not a surprise, and Neuralstem stated that it planned to produce more data later in the year, at scientific conferences for example.
One analyst who wrote on the Neuralstem press release compared the reported ALSFRS-R changes in the Phase 2 clinical trial to a historical dataset, PRO-ACT. According to their interpretation, when the data from all participants are analyzed together against the historical control group, it indicates that treatment may have had an overall adverse effect on disease progression. Such use of historical controls in lieu of placebo control arms in drug trials remains a controversial topic. Principle Investigator, Eva Feldman, MD, PhD, states clearly in the company's release that she intends to move the proposed treatment into a larger controlled trial, which could be interpreted as one including a placebo or standard of care arm. She suggested that the trial may open for enrollment as early as this summer.
It is the opinion of the ALS Therapy Development Institute that the Phase 2 clinical trial was not designed to measure the efficacy of NSI-566. However, we are encouraged by this additional trial finding the treatment and treatment procedure to be safe and tolerable, in general, in people diagnosed with ALS. We believe that Neuralstem should continue its efforts with this treatment, including the organization and execution of additional clinical trials.