Reductions in NfL were also associated with changes on ALSFRS-R scores.
NurOwn cell therapy significantly elevated markers of neuroprotection and lowered markers of neuroinflammation and neurodegeneration, including neurofilament light (NfL) compared to placebo in treated patients with amyotrophic lateral sclerosis (ALS).1
The new data, from a phase 3 trial (NCT03280056), were presented at the 2023 ALS and Related Motor Neuron Diseases Gordon Research Conference, held in Les Diablerets, Vaud, Switzerland, on July 1-2, 2023, by Stacy Lindborg, PhD, co-chief executive officer, BrainStorm Cell Therapeutics.
"It's well known that in ALS, accounting for disease characteristics such as site of onset, time from first symptom to treatment and baseline physical function are important to understanding the treatment effect in clinical trials given the great heterogeneity in the disease, which can influence prognosis," Lindborg said in a statement.1 "The data we presented at the Gordon Research Conference show that it is equally important to examine biomarker data, particularly neurofilament light, which is a predictor of disease progression. Treatment-driven reductions in NfL are associated with better clinical outcomes in ALS."
The new analysis examined 16 pro-inflammatory/anti-inflammatory, eight neurodegeneration, and nine neuroprotection biomarkers from cerebrospinal fluid of participants in the phase 3 trial. Investigators found that 3 biomarkers predicted clinical outcomes, including change in Galectin-1 and baseline biomarkers NfL and LAP/TGFβ1. Covariates of baseline disease characteristics were also found to be important in the analysis of clinical outcomes (all P <.001). After accounting for baseline disease covariates, treated participants had reduced NfL values from baseline to week 20 compared to placebo (P <.05).1
Furthermore, NfL baseline levels were predictive of disease progression in ALS. Participants with greater decline from baseline at week 28 as measured by ALSFRS-R total score had higher baseline NfL values (r=-0.33, P=.0064). Causal inference using a natural disease progression model also showed a relationship between reductions in NfL at week 20 and changes in ALSFRS-R at week 28 from baseline (r = -0.365, P = .087).1
NurOwn will be discussed by the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee in a meeting scheduled for September 27, 2023.2 The PDUFA date for BrainStorm's biologics license application review is set for December 8, 2023.
New analyses announced in 2022 prompted BrainStorm to submit the BLA despite the phase 3 trial failing to meet its primary endpoint in 2021 of responder rates on ALSFRS-R scores in all stages of disease progression.3 A newer erratum has since revealed that analyses that adhered more closely to prespecified sub-analyses showed statistically significant improvements (P = .050) of more than 2 points on ALSFRS-R scores in participants with a baseline score of at least 35. Despite the new data, BrainStorm later received a refusal to file letter from the FDA, which the company later met with in a Type A Meeting, which garnered the Advisory Committee Meeting.