Stem Cell Therapy Shows Intriguing Topline Data in Phase 2 MS Study

Ralph Kern MD MHSc

The autologous mesenchymal stem cell (MSC) therapy NurOwn was safe and led to improvements in function and cognition at 28 weeks compared with baseline for patients with progressive multiple sclerosis (MS), according to topline phase 2 findings released in a statement from BrainStorm Cell Therapeutics, the company developing the treatment.

The phase 2 study enrolled 20 patients, with 18 treated and 16 completing the full course of the study. According to the company, from baseline there was a 25% improvement in timed 25-foot walk (T25FW) for 14% of treated patients and a 25% improvement in 9-hole peg test (9-HPT) was observed for 13% of treated patients. Of the 18 treated patients, these percentages equal 2.52 and 2.34 patients for each end point, respectively. Additional details were not provided on these data; however, in a matched historical control group from the CLIMB registry, these end points were not met by any patients, the company noted.

"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," Ralph Kern MD MHSc, president and chief medical officer of Brainstorm, said in a statement. "We plan to present a detailed summary of the study outcomes at an upcoming scientific meeting, publish our findings in a peer-reviewed journal, and consider how best to advance NurOwn in progressive MS."

NurOwn consists of MSC that have been enhanced and expanded ex vivo to 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. In the phase 2 study, doses of NurOwn consisted of 100 to 125 million autologous MSC-NTF cells.

The mean age of the treated patients in the study was 47 years and the mean baseline Expanded Disability Status Scale (EDSS) score was 5.4. All patients had primary or secondary progressive MS, were relapse-free for at least 6 months prior to study entry, and were able to walk 25 feet in 60 seconds or less. Outcomes from enrolled patients were compared with 48 patients was a match clinical cohort from the CLIMB Study.

Overall, there were no deaths in the study or adverse events (AEs) related to the worsening of MS, according to the company. Of the 20 patients enrolled, 2 never received treatment and 2 patients discontinued the study prior to completing all 3 doses due to unspecified procedure-related AEs.

In addition to T25FW and 9-HPT, from baseline to week 28 Brainstorm noted that 38% of treated patients (6.84 of 18) showed at least a 10-point improvement in 12 item MS Walking Scale (MSWS-12). Additionally, from baseline to week 28 there was at least an 8-letter improvement in low contrast letter acuity test (LCLA) for 47% of patients (8.46 of 18) and 67% (12 of 18) experienced at least a 3-point improvement in the symbol digit modality test (SDMT).

The company noted that all treated patients experienced a 10% improvement in T25FW from baseline to week 28. This was compared with worsening in 1.8% of those in the CLIMB registry. Moreover, all patients had a 4.8% improvement in 9-HPT in their dominant hand from baseline to week 28. In the registry, there as a 1.4% decline in 9-HPT. Brainstorm said that 6% of NurOwn-treated patients experienced an improvement in MSWS-12 from baseline to week 28.

Early signs of increases in VEGF and HGF were noted following treatment with NurOwn along with decreases in the neuroinflammatory biomarkers MCP-1, SDF-1, and osteopontin. Additional biomarker data are being further analyzed for presentation at a future medical meeting, the company noted.

"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 of Experimental Therapeutics, Cleveland Clinic Mellen Center for MS, said in a statement.