NurOwn Meets Primary End Point in Primary Progressive MS

Author(s):

Patients treated with NurOwn showed a mean improvement from baseline of 10% in timed 25-foot walk and a 4.9% improvement from baseline on the 9-hole peg test dominant hand.

Chaim Lebovits

BrainStorm Cell Therapeutics announced that the company’s phase 2 trial evaluating NurOwn (autologous mesenchymal stromal cells secreting neurotrophic factors [MSC-NTF] cells) met its primary end point of safety in the treatment of progressive multiple sclerosis (MS).¹

The 28-week, open-label trial (NCT03799718) enrolled 20 patients with primary and secondary progressive MS who were given 3 repeated administrations of NurOwn, each 2 months apart. Additional secondary efficacy data and detailed cerebrospinal fluid and blood biomarker analyses are still underway and will be reported at an upcoming scientific meeting, according to BrainStorm.

A total of 18 patients were treated and 16 (80%) completed the study. Procedure-related adverse events (AEs) resulted in 2 patients discontinuing. There were no study deaths or AEs related to MS worsening.

"This is an extremely exciting outcome, as it demonstrates the potential of our proprietary cell therapy NurOwn in progressive MS and expands the body of evidence supporting the NurOwn technology platform in neurodegenerative disease,” Chaim Lebovits, chief executive officer, BrainStorm, said in a statement.

FIGURE. NurOwn in Progressive MS

Efficacy outcomes of NurOwn were compared with a 48-patient matched clinical cohort from the Comprehensive Longitudinal Investigations in MS at the Brigham & Women’s Hospital (CLIMB) study. All told, 38% of patients who received the treatment showed at least a 10-point improvement in the 12-Item MS Walking Scale (MSWS-12) from baseline to week 28.

In addition to MSWS-12, patients were also recorded on cognitive and function measures such as timed 25-foot walk (T25FW), 9-hole peg test (9-HPT), Low Contrast Letter Acuity (LCLA), and Symbol Digit Modalities Test (SDMT). From baseline to 28 weeks, prespecified 25% improvements in the T25FW and 9-HPT were observed in 14% and 13% of NurOwn treated patients, respectively, compared to 0% of those in prespecified matched cohorts.

Improvements of at least 8 letters on LCLA, a visual function test, were shown in 47% of treated patients across the 28 weeks. Additionally, 67% showed at least a 3-point improvement in the SDMT, a measure of cognitive processing.

Researchers also documented that the NurOwn-treated group had a mean improvement from baseline of 10% in T25FW and a 4.8% improvement from baseline on the 9-HPT dominant hand, compared to 1.8% and 1.4% worsening, respectively, in matched historical controls from the CLIMB registry.

"These positive results indicate the potential of MSC-NTF cells to lessen inflammatory mechanisms, promote repair, and restore function in progressive MS, a condition for which there is great need for effective therapy,” Jeffrey Cohen, MD, director, Experimental Therapeutics, Mellen Center for MS, Cleveland Clinic, said in a statement. Cohen reported no disclosures related to the study.

Just prior to the 3 consecutive time points of administration of NurOwn, increases in neuroprotective molecules (VEGF, HGF) and decreases in neuroinflammatory biomarkers (MCP-1, SDF-1, and osteopontin) were observed.

There are currently no FDA-approved autologous cell therapy options for MS, and the therapeutic landscape of options for those with progressive disease remains limited. The investigational new drug application for the phase 2 clinical trial was accepted by the FDA in December 2018.²

BrainStorm has also evaluated the therapy in patients with amyotrophic lateral sclerosis (ALS). Most recently, the FDA provided feedback to the company, concluding that the currently level of data does not cross the threshold of substantial evidence to support a biologics license application (BLA).³ In November 2020, the company announced topline results from its phase 3 trial, demonstrating that treatment with NurOwn was generally well-tolerated in a population of rapidly progressing patients with ALS. While showing a numerical improvement in the treated group compared to placebo across the primary and key secondary end points, the trial did not reach statistically significant results.⁴

REFERENCES

1. BrainStorm announces positive topline data in phase 2 study evaluating NurOwn as a treatment for progressive MS. News release. BrainStorm Cell Therapeutics. March 24, 2021. Accessed March 28, 2021. https://www.prnewswire.com/news-releases/brainstorm-announces-positive-topline-data-in-phase-2-study-evaluating-nurown-as-a-treatment-for-progressive-ms-301254709.html

2. FDA Accepts BrainStorm’s NurOwn® IND Application for Progressive Multiple Sclerosis. News release. BrainStorm Cell Therapeutics Inc. December 17, 2018. Accessed March 28, 2021. https://www.globenewswire.com/news-release/2018/12/17/1667840/0/en/FDA-Accepts-BrainStorm-s-NurOwn-IND-Application-for-Progressive-Multiple-Sclerosis.html

3. BrainStorm announces high-level FDA feedback on NurOwn ALS clinical development program. News release. BrainStorm Cell Therapeutics. February 22, 2021. Accessed March 28, 2021. https://ir.brainstorm-cell.com/2021-02-22-BrainStorm-Announces-High-Level-FDA-Feedback-on-NurOwn-R-ALS-Clinical-Development-Program

4. BrainStorm announces topline results from NurOwn phase 3 ALS study. News release. BrainStorm Cell Therapeutics. November 17, 2020. Accessed March 28, 2021. https://ir.brainstorm-cell.com/2020-11-17-BrainStorm-Announces-Topline-Results-from-NurOwn-R-Phase-3-ALS-Study