Results from a phase 2 study showed the safety and provided the preliminary evidence for the efficacy of BrainStorm Cell Therapeutics’ NurOwn treatments in people with progressive multiple sclerosis. Additionally, biomarker analyses showed consistent treatment effects in neuroinflammation and neuroprotection pathways.

Twenty participants were enrolled into the trial, with 17 receiving all three scheduled NurOwn treatments. The mean age of study participants was 47 years with a mean Expanded Disability Status Scale score of 5.4 at screening. Results from the trial were compared to 48 matched control patients who were selected from the Comprehensive Longitudinal Investigation of Multiple Sclerosis registry at the beginning of the trial.

Treatment with NurOwn resulted in improvements in some patients, as defined by response criteria, across all endpoints measured. These endpoints included timed 25-foot walk speed, 9-hole peg test, multiple sclerosis walking scale, symbol digit modality test, and low contrast letter acuity. These observed improvements diverged from what was seen in matched patients with progressive MS from the CLIMB registry.
 

• 19 percent of treated trial participants were responders, compared to 4 percent of the matched CLIMB registry patients. 
• 38 percent of treated trial participants showed an improvement of 10 points or more in the 12-item MSWS (data for this endpoint were not collected by the CLIMB registry).
• 27 percent of treated trial participants showed an improvement of 8 letters or more in LCLA binocular at a 2.5 percent contrast threshold, compared to 6 percent of the matched CLIMB registry patients.
• 67 percent of treated trial participants showed an improvement of 3 points or more in the SDMT, compared to 18 percent of the matched CLIMB registry patients.
• 47 percent of treated trial participants showed an improvement of 8 points or more in LCLA binocular at a 1.25 percent contrast threshold (data for this endpoint were not collected by the CLIMB registry).

Across all participants, improvements in function as measured by LCLA, SDMT, and MS Functional Composite were observed. Mean improvements from baseline of 3.3 points in the LCLA binocular (2.5 percent contrast), 3.8 points on the SDMT, and 0.18 points in MSFC were observed in treated trial participants. The corresponding changes in matched CLIMB registry patients estimated at 28 weeks showed declines in function on the LCLA and MSFC. The average change in function decline as measured by T25FW, 9HPT, and EDSS across all treated trial participants demonstrated stabilization of functional decline, with similar or slightly worse findings observed in the matched CLIMB registry patients for the same endpoints.

There were no adverse events related to worsening of MS disease and no clinically significant changes in safety lab results/vital signs, confirming NurOwn's favorable safety profile. Two patients developed symptoms of low back and leg pain, consistent with arachnoiditis, occurring in one of three treatments in both participants. Treatment also consistently resulted in increases in cerebrospinal fluid neuroprotective factors and reductions in inflammatory biomarkers, confirming NurOwn's proposed mechanism of action in progressive MS.

According to Dr. Ben Thrower, medical director of the Andrew C. Carlos MS Institute at Shepherd Center in Atlanta and MS Focus senior medical advisor, “Current management of MS focuses on treating relapses, managing symptoms, and preventing future progression of disability. There is a fourth goal that we are moving closer to each day. That would be neural repair and the reversal of disability. This current trial represents a step towards that goal. Mesenchymal stem cells represent one potential avenue for restoring function to those with MS-related disability. Small, early trials like this will serve to guide us towards larger studies and, hopefully, an FDA-approved option in the future.”

The NurOwn technology platform represents a therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors. Autologous MSC-NTF cells are designed to effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression.

The results were published in Multiple Sclerosis Journal.