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NurOwn Treatment Shows Positive Results in Phase 2 Study of Progressive Multiple Sclerosis

SAP Partner | <b>Cleveland Clinic</b>

Treatment with NurOwn resulted in response on several secondary outcomes, including timed 25-foot walk, 12-item multiple sclerosis walking scale, and low contrast letter acuity, among others.

BrainStorm Cell Therapeutics announced the peer reviewed publication of its phase 2 trial evaluating NurOwn (autologous mesenchymal stromal cells secreting neurotrophic factors [MSC-NTF] cells) to treat patients with progressive multiple sclerosis (MS), a disease with limited number of approved therapies.1,2

All told, findings from the single-arm, open-label study (NCT03799718) showed clinically meaningful improvements across end points such as timed 25-foot walk speed (T25FW), 9-hole peg test (9HPT), multiple sclerosis walking scale (MSWS), Symbol Digit Modality Test (SDMT), and low contrast letter acuity (LCLA). The improvements from in NurOwn-treated patients were compared and confirmed with 48 matched controls from the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) registry.

"We were pleased that the study's initial results showed efficacy in patients with progressive MS," lead investigator Jeffrey Cohen, MD, director, Mellen Center for MS Treatment and Research, Cleveland Clinic, said in a statement.1 "There are both promising biological and preliminary clinical signals of a treatment effect that will require confirmation in a randomized trial."

A total of 20 participants, aged 18 to 65 years, were enrolled into the phase 2 trial, with 17 receiving all 3 scheduled NurOwn treatments. Eligible participants had no relapse for 6 months prior to screening, baseline Expanded Disability Status Scale (EDSS) scores between 3.0 and 6.5, and had the ability to walk 25 feet in 60 seconds or less. After an approximate 10-week pre-treatment period that included an outpatient bone marrow aspiration to obtain mesenchymal cells for manufacturing, patients received intrathecal administrations of autologous MSC-NTF cells at weeks 0, 8, and 16, followed by a 12-week post-treatment observation period.

Of the 20 participants included, 2 discontinued because of procedure-related adverse events, including feeling cold, muscle weakness, and pyrexia in 1 patient and arachnoiditis in another. Two treated participants developed symptoms of low back and leg pain, considered serious treatment-emergent adverse events, and consistent with a diagnosis of arachnoiditis. Both participants were treated with epidural cortisone injections and analgesics, and the symptoms completely resolved in 1 participant, who subsequently completed the third intrathecal treatment without the AE recurring. In the second case, the symptoms occurred only after the third intrathecal treatment and did not fully resolve.

In total, 19% (3 of 16) of pooled participants reached a clinical response of 25% or greater in T25FW speed or 9HPT. In contrast, less than 5% of the matched CLIMB cohort achieved any of these pre-specified outcomes. Although data for MSWS were not collected by the CLIMB registry, 38% (6 of 16) of NurOwn-treated patients showed at least a 10-point improvement from baseline in the 12-item MSWS. Additionally, 77% (10 of 15) of patients showed at least a 3-point improvement in the SDMT.

"Having these data peer reviewed and published in the prestigious Multiple Sclerosis Journal is an important step in the evaluation of NurOwn in progressive MS," Chaim Lebovits, chief executive officer, BrainStorm Cell Therapeutics, said in a statement.1 "Thanks to their efforts and those of the BrainStorm team, we believe we are closer to providing a meaningful treatment option for those with progressive MS."

Continued results from secondary and exploratory efficacy end points showed that 47% (7 of 15) of the treated cohort had at least an 8-letter improvement in LCLA at the 1.25% contrast threshold, and 27% (4 of 15) showed at least an 8-letter improvement at a 2.5% contrast threshold. None of the participants with baseline EDSS scores less than 5.5 demonstrated an improvement of at least 1.0 point, while 30% (3 of 10) of participants with baseline EDSS scores above 5.5 showed an improvement of at least 0.5 points. From baseline to week 28, MSC-NTF cell-treated patients showed a median change of –0.05 feet/second in T25FW. MSWS-12 and EDSS showed no median change at the end of the treatment period.

Treatment with NurOwn resulted in consistent trends for increases in the percent change for cerebrospinal fluid neuroprotective factors such as vascular endothelial growth factor A, hepatocyte growth factor, neural cell adhesion molecule 1, follistatin, leukemia inhibitory factor, and fatuin-A, from baseline to week 16. Similarly, consistent trends for a reduction in percentage change in inflammatory biomarkers such as monocyte chemoattractant protein-1, soluble stromal cell-derived factor 1, osteopontin, and soluble CD27, were also observed. Neurodegeneraitve biomarkers such as neurofilament light, phosphorylated neurofilament heavy chain, and glial fibrillary acidic protein did not show consistent changes following treatment.

"This publication provides preliminary evidence of NurOwn's potential to modify functional outcomes in progressive MS, which we believe warrants further study," coinvestigator Ralph Kern, MD, MHSc, president and chief medical officer, BrainStorm Cell Therapeutics, said in a statement.1 "In addition, consistent changes in cerebrospinal fluid neuroinflammation and neuroprotection biomarkers reveal how NurOwn may impact disease mechanisms in progressive MS and are complementary to biomarker results observed in our Phase 3 ALS trial. These observations provide further support for NurOwn as a platform technology with potential broad applications and will bolster BrainStorm's efforts to bring much needed solutions to patients with progressive MS, ALS, and other neurodegenerative diseases."

Most recently, in mid-August, following corrections to its phase 3 trial that further boosted results, the company announced it will be submitting a biologics license application for NurOwn to treat amyotrophic lateral sclerosis, a decision that comes more than a year after the FDA recommended against it.3

REFERENCES
1. BrainStorm Cell Therapeutics announces peer reviewed publication of results from the NurOwn phase 2 progressive MS trial in Multiple Sclerosis Journal. News release. BrainStorm Cell Therapeutics. September 15, 2022. Accessed September 15, 2022. https://ir.brainstorm-cell.com/2022-09-15-BrainStorm-Cell-Therapeutics-Announces-Peer-Reviewed-Publication-of-Results-from-the-NurOwn-R-Phase-2-Progressive-MS-Trial-in-Multiple-Sclerosis-Journal
2. Cohen JA, Lublin, Kern R, et al. Evaluation of neurotrophic factor secreting mesenchymal stem cells in progressive multiple sclerosis. Mult Scler J. Published online September 14, 2022. doi:10.1177/13524585221122156
3. BrainStorm Cell Therapeutics announces second quarter 2022 financial results and provides a corporate update. News release. BrainStorm Cell Therapeutics. August 15, 2022. Accessed September 15, 2022. https://ir.brainstorm-cell.com/2022-08-15-BrainStorm-Cell-Therapeutics-Announces-Second-Quarter-2022-Financial-Results-and-Provides-a-Corporate-Update