NurOwn Passes Interim Phase III ALS Study Safety Analysis

Carlayne Jackson, MD, professor of neurology and otolaryngology at the University of Texas Health Science Center San Antonio

Carlayne Jackson, MD

The promising mesenchymal stem cells (MSC) therapy NurOwn has passed an interim safety analysis for the first 31 patients with amyotrophic lateral sclerosis (ALS) enrolled in an ongoing phase III study, according to an independent data safety monitoring board (DSMB).

The phase III study enrolled its first patient in October 2017, and has since completed enrollment for 82 patients with rapidly progressing ALS. The study plans to include 200 total participants, which should be reached by the middle of 2019, said BrainStorm Cell Therapeutics, the company developing the MSC therapy.

The primary outcome measure for the study, which is enrolling across 6 institutions, is safety and efficacy by ALS functional rating scale (ALSFRS-R). The company plans to submit a biologics license application to the FDA for approval, once a final analysis is complete.

“The DSMB appreciates the continued commitment of Brainstorm and the research teams to conducting this trial in such an exemplary manner,” Carlayne Jackson, MD, chairperson of the DSMB and professor of neurology and otolaryngology at the University of Texas Health Science Center San Antonio, said in a statement. “We commend them on their outstanding enrollment and the quality of data collection.”

NurOwn consists of MSC that have been enhanced and expanded ex vivo to several secrete several neurotrophic factors (NTFs). The autologous cells, which secrete primarily GDNF, brain-derived NTF, VEGF, and hepatocyte growth factor (HGF), are administered in 3 intrathecal transplantations, each 2 months apart. The company noted that of the enrolled 82 patients, most had received the first 2 intrathecal injections, with some completing all 3.

"We are very pleased the DSMB has found no safety concerns that would require modification to the NurOwn ALS phase III protocol," Ralph Kern, MD, MHSc, chief operating officer and chief medical officer of BrainStorm, said in a statement. "This represents an important clinical advancement for BrainStorm and for NurOwn as a viable cellular therapy approach for ALS patients.”

Prior to the phase III trial, promising findings were demonstrated in a phase II trial, especially for patients with rapidly progressing ALS. The study randomized 48 patients with ALS to receive NurOwn (n = 36) or placebo (n = 12). Most enrolled patients were male (72.9%) and had a mean age of 51.1 years.

Overall, significantly more patients treated with NurOwn had a ≥1.5-point improvement in ALSFRS-R compared with placebo at 4 weeks (P = .02) and 12 weeks (P = .08). There were increases in cerebrospinal fluid (CSF) NTFs at 2 weeks’ post treatment, specifically for VEGF, HGF, and Leukemia inhibitory factor (LIF). These spikes were accompanied by decreases in several inflammatory markers in the CSF, such as MCP-1 and SDF-1.

Overall, improvements of ≥0.375-point were experienced by patients treated with NurOwn across all 4 subscale domains per month. For the ALSFRS-R bulbar domain specifically for rapid progressors, at week 4 there was a ≥0.375-point improvement for 47% of patients treated with the cell therapy arm compared with none in the placebo group (P = .08). At week 8 and 16, this remained 47% versus 0% for NurOwn and placebo, respectively. By week 24, 40% of patients had a ≥0.375 point improvement in the bulbar domain with NurOwn versus none with placebo (P = .09).

For the fine motor domain for rapid progressors, 87% showed improvement of ≥0.375 with NurOwn compared with 40% for placebo at 2 weeks (P = .07). There were also improvements for the gross motor and breathing domains; however, these did not reach statistical significance.

The MSC therapy was well tolerated, with no patients discontinuing the study due to treatment-related adverse events (AEs). The most common AEs, which were mostly grade 1 to 2 in severity, for the cell therapy versus placebo, respectively, were headache (80.6% vs 66.7%), back pain (72.2% vs 8.3%), pyrexia (33.3% vs 0%), arthralgia (33.3% vs 0%), injection site pain (27.8% vs 8.3%), and constipation (25% vs 8.3%).

“BrainStorm is focused on completing the NurOwn ALS phase III study and to bringing a much needed treatment option to ALS patients,” Chaim Lebovits, president and CEO of BrainStorm, said in a statement. “We welcome the DSMB’s review which confirms the safety profile of NurOwn following repeat dose intrathecal administration.”

The FDA has granted NurOwn an orphan drug designation and a fast track designation for ALS, which will help speed up development for the cell therapy. In addition to ALS, preclinical work is also focusing on the treatment for multiple sclerosis, Parkinson disease, Huntington disease, autism spectrum disorder, and peripheral nerve injury.

Kern R, Cudkowicz M, Berry J, et al. NurOwn Phase 2 ALS Trial: ALSFRS-R Improvement is Reflected in Subscale Domains. Presented at: 2018 American Academy of Neurology Annual Meeting, Los Angeles, CA, April 21-27, 2018. Abstract S38.002.