NeuroGenesis and Hadassah Medical Center Report Positive NF-L Biomarker Results from a Phase 2 Study in Progressive Multiple Sclerosis Treated with NG-01 Cells Therapy
- Results, published in Stem Cells Translational Medicine, show significant reduction of NF-L, a biomarker for neuronal damage, in patients with progressive multiple sclerosis after treatment with NG-01 stem cells
JERUSALEM, March 1, 2022 /PRNewswire/ -- NeuroGenesis, a clinical-stage biopharmaceutical company advancing innovative cell therapies to combat myelin-related neurodegenerative diseases, and Hadassah Medical Center announced today positive results from a placebo-controlled Phase 2 clinical trial assessing the impact of NG-01 autologous proprietary subpopulation of bone marrow cells on the expression levels of NF-L, a commonly-used biomarker for multiple sclerosis (MS) and other neurogenerative diseases, in patients with progressive MS. The trial was headed by Prof. Dimitrios Karussis, together with Dr. Petrou Panayiota and Dr. Ibrahim Kassis, all from Hadassah Medical Center in Jerusalem. The results were recently published in Stem Cells Translational Medicine.
NF-L is a protein released into the cerebrospinal fluid (CSF) by damaged neurons and is a reliable biomarker for neuronal damage in patients with MS and other neurodegenerative diseases. High levels of NF-L are consistently found in the CSF of MS patients and can be used as a biomarker of MS disease activity as well as of the response to various MS-treatments.
The Phase 2, randomized, double-blind, placebo-controlled, clinical trial assessed the safety, tolerability, and efficacy of transplantation of NG-01 in people with progressive MS. The study enrolled 48 participants with progressive MS which were randomized into 3 groups, receiving either an intrathecal (IT) or intravenous (IV) NG-01 injection, or a placebo injection. CSF samples were obtained from the study participants at baseline and at 6 months following treatment with NG-01 or placebo, and the level of the NF-L biomarker was assessed in each sample. The samples of 4 patients were not technically testable for NF-L.
The results show that CSF concentrations of NF-L were exceptionally high in almost all patients (>10,000pg/ml in 8/15 patients in the IT group, 7/15 patients in the IV group and 7/14 patients in the placebo group), indicating an active and aggressive disease at baseline, as also depicted by the deterioration in the Expanded Disability Status Scale (EDSS) and MRI evaluation prior to the treatment. In the IT group, at 6 months following treatment the levels of NF-L were significantly reduced compared to the baseline pre-treatment measurements (median reduction: 63.5 %). A smaller, insignificant reduction was seen in the IV group, whereas NF-L levels actually increased indicating deterioration in the placebo group (median increase of 47.5 %). Nine out of 15 tested patients in the IT group had a reduction in NF-L levels of more than 50 %, compared to only 1 out of 15 in the placebo group.
Reduction of NF-L levels correlated with significant functional improvement. Eight out of the 9 patients in the IT group that experienced a >50% reduction in the NF-L levels were stable or improved in EDSS at 6 months and experienced an improved disability score even after a follow up of 12 months (end of study). In the same study, Hadassah researchers also reported a clear trend of reduction in the proinflammatory chemokine in the CSF following intrathecal treatment with NG-01, indicating local immunomodulation in the CNS, induced by the stem cell therapy.
The NF-L results provide the first reported objective evidence of neuroprotection induced by the intrathecally injected stem cells and are in line with the encouraging NG-01 clinical results in two long term trials in progressive MS and ALS published in Frontiers of Neurology[i] and Frontiers in Bioscience[ii], respectively. The MS trial showed that repeated NG-01 treatments were safe at the short/intermediate term and induced clinical benefits, that lasted for up to four years, especially in patients treated with more than two NG-01 injections. More information on the long-term trials can be found in www.ClinicalTrials.gov (identifier of the MS trial: NCT04823000 and identifier of the ALS trial: NCT04821479).
"Progressive MS is a debilitating disease without effective treatment options that can substantially suppress the progression of disability," said Professor Dimitrios Karussis, lead principal investigator and Director of MS Center at Hadassah Medical Center, Jerusalem. "This novel trial evaluated not only the clinical effects induced by the stem cell therapy, but also the effects on the most reliable and accepted biomarker of neuro-degeneration, NFL. We therefore believe that our findings are extremely encouraging and taken together with the long-term clinical results, that showed stabilization and even functional improvement in 22 out of the 24 participants up to 4 years after the initiation of treatment, provide substantial optimism for the future of management of progressive MS and neurodegenerative diseases in general."
"We are extremely pleased to witness the significant protective effect of our NG-01 cells on NF-L and the very encouraging long term clinical results in MS and ALS," said Tal Gilat, CEO of NeuroGenesis. "We are currently working on expanding our manufacturing capacity in the US in preparation for our multi-center Phase 2b trial in secondary progressive MS that is planned to begin in late 2022."
NeuroGenesis' technology entails collecting bone marrow from the patient. Then by utilizing a proprietary process, a unique subpopulation of bone marrow cells is identified, cultured and enhanced towards remyelinating biofactory cells (NG-01) that also possess neurotrophic and neuroprotective properties. The NG-01 cell population is injected directly into the central nervous system (through the cerebrospinal fluid), where the cells home-in on the damaged area, take up residence and produce significant amounts of neurotrophic factors.
NeuroGenesis is developing cell therapy for neurodegenerative diseases based on a unique approach for sustained delivery of high levels of remyelinating growth factors using the patient's own stem cells. The Company's lead product is NG-01 for the treatment of progressive Multiple Sclerosis, (in which a placebo-controlled Phase 2 study has been completed and recently published). NG-01 was also tested in two successful Phase 2a trials in ALS patients. Up to today, more than 150 progressive MS and ALS patients from around the world have been treated with NeuroGenesis' products via clinical trials (Phase 1 and Phase 2) and compassionate use treatments. The technology was licensed from Hadasit, the Technology Transfer Company of Hadassah Medical Organization in Jerusalem, Israel.
About Hadassah and Hadasit
For more than a century, Hadassah has set the standard of excellence for medical care and research in Israel. Our doctors and scientists are on the frontlines, uniquely positioned to pinpoint ever-evolving medical needs. Their experience and ingenuity have yielded new ideas with huge potential in all areas of medicine, including therapeutics, diagnostic medical devices, and digital health. Hadasit is the technology transfer company of Hadassah Medical Center in Jerusalem. We transform the cutting-edge research coming out of Hadassah into marketable medical technologies. We turn ground-breaking ideas into viable products and services that can change the world and better humanity.
[i] Karussis et al. (2021) Long-Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cell Injections in Patients With Progressive Forms of Multiple Sclerosis. Frontiers in Neurology May 2021 | Volume 12 | Article 639315; doi: 10.3389/fneur.2021.639315
[ii] Karaussis et al. (2021) A phase II clinical trial with repeated intrathecal injections of autologous mesenchymal stem cells in patients with amyotrophic lateral sclerosis. Frontiers in Biosciences. 2, 1-13, DOI:10.52586/?.
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SOURCE NeuroGenesis; Hadassah Medical Center