NurOwn cell therapy led to significant improvements in the physical abilities, vision, and cognition of people with progressive multiple sclerosis (MS) in a Phase 2 clinical trial, top-line data show.
In addition to these positive efficacy results, BrainStorm Cell Therapeutics, NurOwn’s developer, announced that its cell-based therapy showed a good overall safety profile.
Trial participants received three injections, with two-month intervals between each treatment. The company reported that levels of neuroprotective molecules increased in the treated MS patients while neuroinflammatory biomarkers decreased.
“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, CEO of BrainStorm, said in a press release.
NurOwn is produced from a patient’s own bone marrow-derived mesenchymal stem cells (MSCs). MSCs are grown under specific conditions that stimulate cells to release neurotrophic factors (NTFs). These factors induce the growth and development of brain cells.
MSC-NTF cells are designed to deliver NTFs and other important factors directly to the site of damage to slow the progression of the disease.
Altogether, 20 primary and secondary progressive MS patients, ranging in age from 18 to 65, were enrolled in the trial. All patients could walk 25 feet in 60 seconds (one minute) or less and had not relapsed within six months of enrollment. The average age of the group was 47, and a majority of the participants (56%) were female.
Participants were allowed to be on a stable dose of disease-modifying therapy during the trial.
Three injections of 100-125 million MSC-NTF cells were given intrathecally, or directly into the spinal canal. There were two-month intervals between each treatment, and patients were followed for a total of 28 weeks (about seven months) after the first injection.
The primary endpoint, or goal, of the trial was safety, and the second endpoint was efficacy.
In total, 18 of 20 patients were treated with NurOwn, and of these, 16 (80%) completed the trial. Two of the 18 patients dropped out of the study because of adverse events (AEs) or side effects caused by the procedure.
There were no deaths related to the study or AEs due to worsening of MS symptoms.
For efficacy, the trial’s data were compared with those of 48 matched patients from a clinical group involved in the Comprehensive Longitudinal Investigations in MS study, known as CLIMB, done at the Brigham & Woman’s Hospital in Boston.
Several tests were performed to evaluate the patients’ functional, mental and visual abilities. These were the 9-hole peg test (9-HPT), the timed 25-foot walk (T25-FW), the 12-item MS Walking Scale (MSWS-12), the Symbol Digit Modality Test (SDMT), and an eye exam known as Low Contrast Letter Acuity (LCLA).
Among the NurOwn-treated patients, 14% showed prespecified 25% improvements in the T25-FW by 28 weeks. Likewise, 13% of MS patients treated with NurOwn showed improvements by 25% in the 9-HPT. None of the matched controls in the CLIMB registry showed improvements in these measures.
NurOwn-treated patients also showed an average improvement of 10% in T25-FW and 4.8% on the 9-HPT, in comparison with their performance prior to treatment. In contrast, in matched controls from the CLIMB registry, a worsening of 1.8% in T25-FW, and 1.4% on 9-HPT, were observed.
A minimum of a 10-point improvement was obtained by 38% of NurOwn-treated patients on the MSWS-12, a patient self-assessment survey that evaluates walking ability. By the end of the 28-week study, treated patients showed a 6% improvement in MSWS-12 compared with the start of the study.
Furthermore, 47% of NurOwn-treated patients achieved a minimum of an eight-letter improvement in the vision test, known as LCLA, while 67% showed at least a three-point improvement in the cognitive processing speed test SDMT.
Biomarkers from the cerebrospinal fluid (CSF) were analyzed before each NurOwn injection. While levels of molecules with neuroprotective effects such as VEGF and HGF increased, proteins associated with neuroinflammation — namely MCP-1, SDF-1, and osteopontin — decreased.
“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,” said Jeffrey Cohen, MD, director of experimental therapeutics at the Cleveland Clinic Mellen Center for MS.
“The unprecedented results of this phase 2 clinical trial provide strong support for the potential of NurOwn to address the unmet clinical and biological need in progressive MS,” said Ralph Kern, MD, president and chief medical officer of Brainstorm.
“Currently, few therapeutic options exist to address the relentless clinical progression and disability accumulation, ongoing compartmentalized and intrathecal CNS inflammation, and progressive loss of neural function in progressive MS,” Kern said.
Brainstorm plans to present its findings on efficacy and biomarker analyses at an upcoming scientific meeting and to publish the results in a peer-reviewed journal.
The company received a grant from the National MS Society to support this Phase 2 clinical trial testing NurOwn in patients with progressive MS. Of note, the company also is testing NurOwn as a therapy for amyotrophic lateral sclerosis.
“We applaud Brainstorm for completion of this first in human trial of NurOwn in progressive MS, and are encouraged by the early indication of safety and effectiveness,” said Mark Allegretta, PhD, vice president of research at the National MS Society. “We’re hopeful that our collaboration will uncover insights into clinically relevant biomarkers that may predict a treatment effect in progressive MS.”
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