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 for which a limited number of approved treatments.1.2
In total, results from the open-label, single-arm study (NCT03799718) showed clinically meaningful improvements on endpoints such as 25-foot Timed Walking Speed (T25FW), 9-Hole Ankle Test (9HPT ), Multiple Sclerosis Walking Scale (MSWS), Symbol Digit Modality Test (SDMT), and Low Contrast Letter Acuity (LCLA). Improvements in NurOwn-treated patients were compared and confirmed with 48 matched controls from the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLMB) registry.
“We were delighted that early study results showed efficacy in patients with progressive MS,” said lead investigator Jeffrey Cohen, MD, director of the Mellen Center for MS Treatment and Research, Cleveland Clinic, in a press release.1 “There are both promising preliminary biological and clinical signals of a treatment effect that will require confirmation in a randomized trial.”
A total of 20 participants, aged 18 to 65, were enrolled in the Phase 2 trial, 17 of whom received the planned 3 NurOwn treatments. Eligible participants had no relapses for 6 months prior to screening, baseline Expanded Disability Status Scale (EDSS) scores were between 3.0 and 6.5, and had the ability to walk 25 feet in 60 seconds or less. After an approximately 10-week pretreatment period that included 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. -period of observation of the treatment.
Of the 20 participants included, 2 dropped out due to adverse events related to the procedure, including feeling cold, muscle weakness and pyrexia in 1 patient and arachnoiditis in another. Two treated participants developed symptoms of low back pain and leg pain, considered serious treatment-related adverse events and consistent with a diagnosis of arachnoiditis. Both participants were treated with epidural cortisone injections and painkillers, and symptoms completely resolved in 1 participant, who then completed the third intrathecal treatment without recurrence of the IE. In the second case, the symptoms appeared only after the third intrathecal treatment and did not completely disappear.
A total of 19% (3 out of 16) of the pooled participants achieved a clinical response of 25% or greater in T25FW or 9HPT speed. In contrast, less than 5% of the matched CLIMB cohort achieved any of these predefined outcomes. Although data on MSWS was not collected by the CLIMB registry, 38% (6 out of 16) of NurOwn-treated patients showed at least a 10-point improvement from baseline in MSWS in 12 items . Additionally, 77% (10 out of 15) of patients showed at least a 3-point improvement in SDMT.
“Having this data peer-reviewed and published in the prestigious Multiple Sclerosis Journal is an important step in the evaluation of NurOwn in progressive MS,” said Chaim Lebovits, CEO of BrainStorm Cell Therapeutics, in a statement.1 “Thanks to their efforts and those of the BrainStorm team, we believe we are one step closer to providing a meaningful treatment option for people with progressive MS.”
Ongoing secondary and exploratory efficacy endpoint results showed that 47% (7 out of 15) of the treated cohort had at least 8 letter improvement in LCLA at the 1.25% contrast threshold, and 27% ( 4 of 15) had at least an 8-letter improvement at a contrast threshold of 2.5%. None of the participants with baseline EDSS scores less than 5.5 demonstrated an improvement of at least 1.0 point, while 30% (3 out of 10) of participants with baseline EDSS scores greater than 5, 5 showed an improvement of at least 0.5 points. From baseline to week 28, patients treated with MSC-NTF cells 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.
NurOwn treatment resulted in consistent trends of increased 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 reduced percent change in inflammatory biomarkers such as monocyte chemoattractant protein-1 , soluble stromal cell-derived factor 1, osteopontin, and soluble CD27 were also observed. Neurodegenerative biomarkers such as neurofilament lumen, phosphorylated neurofilament heavy chain, and glial fibrillary acidic protein did not show consistent changes after treatment.
“This publication provides preliminary evidence for the potential of NurOwn to alter functional outcomes in progressive MS, which we believe merits further study,” said co-investigator Ralph Kern, MD, MHSc, chairman and director. of BrainStorm Cell Therapeutics, in a statement.1 “Furthermore, consistent changes in cerebrospinal fluid neuroinflammation and neuroprotection biomarkers reveal how NurOwn may impact disease mechanisms in progressive MS and are complementary to the biomarker results observed in our phase trial. 3 on ALS. broad applications and will strengthen BrainStorm’s efforts to provide much-needed solutions for patients with progressive MS, ALS and other neurodegenerative diseases.”
Most recently, in mid-August, following corrections to its Phase 3 trial that further improved results, the company announced that it would file a biologics license application for NurOwn to treat lateral sclerosis. amyotrophic, a decision that comes more than a year after the FDA. not recommended.3