Prespecified and post hoc analyses explored the heterogeneity of disease at baseline, with meaningful treatment effect indicated in a subset of patients with less severe ALS.
New analyses from the phase 3 trial (NCT03280056) of the NurOwn technology platform in amyotrophic lateral sclerosis (ALS) were presented at the virtual 4th Annual ALS ONE Research Symposium, November 29-30, with investigators observing the potential for meaningful treatment effect when concentrating on a smaller subset of patients with less severe disease at baseline.1
Results announced by BrainStorm Cell Therapeutics last year confirmed that the phase 3 trial did not meet its statistical primary and secondary end points in slowing ALS disease progression in patients treated with NurOwn (autologous mesenchymal stromal cells secreting neurotrophic factors [MSC-NTF] cells), compared with placebo. New analyses, presented by coprincipal investigator Jonathan Katz, MD, chair, neurology department, and director, Forbes Norris ALS Clinic, California Pacific Medical Center, looked at treatment effect in patients with less severe disease, as the potential treatment effect in this subset was initially protected by randomization. According to investigators, the trial had a higher number of participants with advanced ALS at baseline, defined as an ALSFRS-R score of 25 points or lower.
Investigators identified a subgroup of patients with long to very long survival, as predicted by the European Network for the Cure of ALS (ENCALS) model. Of these patients treated with NurOwn, 33% responded to treatment, compared with 14% of those given placebo. In addition, patients with an ALS Functional Rating Scale (ALSFRS-R) of 35 points or higher at baseline had a higher percentage of responders at 34.6%, compared with 15.6% of those given placebo. According to additional analyses accounting for the ALSFRS-R and the ENCALS categories, efficacy measurements were affected in patients with more severe ALS at baseline.
"These compelling analyses add to the positive momentum behind our ALS program, and we were pleased to have the opportunity to share them with the clinical community at this year's ALS ONE Research Symposium," Stacy Lindborg, PhD, executive vice president, chief development officer, BrainStorm Cell Therapeutics, said in a statement.1
"We are very encouraged by the observation that there appears to be a meaningful treatment effect in patients with less severe disease at baseline that is consistent when using baseline ALS FRS-R scores and the ENCALS model which incorporates additional important disease characteristics that have been shown to be predictive of survival time. We believe this is an important finding, especially since this effect was protected by randomization,” she added.
The NurOwn technology platform targets disease pathways in several neurodegenerative disorders. In March of this year, results from a phase 2 trial (NCT03799718) of the technology in progressive multiple sclerosis were announced, confirming the NurOwn met its primary safety end point. The investigational new drug application for the phase 2 clinical trial was accepted by the FDA in December 2018.2,3
Also in March 2021, the FDA provided feedback to BrainStorm regarding NurOwn’s use in ALS, concluding that the level of data at the time did not cross the threshold of substantial evidence to support a biologics license application. When topline results from the phase 3 trials were announced in November 2020, investigators noted NurOwn was generally well-tolerated in patients with rapidly progressing ALS, and while slower disease progression was identified in patients treated with NurOwn (34.7%), compared with placebo (27.7%), but these results were not statistically significant (P = .453).4,5
“Looking ahead, we are eager to share additional analyses from our phase 3 trial with the clinical community through a peer reviewed publication and remain committed to pursuing the best and most expeditious path forward to bring NurOwn to patients with ALS,” Lindborg said in a statement.1