What does the drug do?
NurOwn (MSC-NTF cells) is a potential therapy investigated by by Brainstorm-Cell Therapeutics. The treatment purifies mesenchymal stem cells from bone marrow extracted from the patients hip bone. The bone marrow-derived stem cells are multiplied outside the body in combination with the NurOwn substance that make the cells produce neurotrophic factors. Neurotrophic factors are though to protect and promote the health of neurones. The cells are then injected back into the same patient in their spinal fluid where it is hoped that they can act as an effective medicine by providing these neurotrophic factors to the nervous system affected by MND. In the placebo group people still had bone marrow removed and an injection into their spinal fluid (but the injection contained no cells) in order to compare the effect of just the physical procedure itself with that of the procedure plus the treated cells.
The Phase 2 randomised, double blind, placebo-controlled trial of NurOwn in the USA looked at the safety and effectiveness of the process in 48 people (36 treated and 12 placebo) and was published in the journal Neurology, titled “A single-dose transplantation of MSC-NTF cells is safe and demonstrated early promising signs of efficacy.”
Results announced in July 2016 revealed that NurOwn treatment was safe and well-tolerated. While not a primary objective of this trial phase, the study reported that NurOwn treatment lowered levels of inflammatory biomarkers in the cerebrospinal fluid (CSF). You can read more about the trial here.
The Phase 3 trial fully enrolled around 200 participants across six sites in the USA to test multiple doses of NurOwn and investigate effectiveness. The primary measurements were to examine safety of repeated intrathecal injections of NurOwn and the ability of NurOwn to slow progression of ALS/MND using a scale called the ALSFRS-R. To determine if NurOwn-treated stem cells were providing the intended biological effect, the (CSF) was measured for biomarkers and neurodegenerative/neuroinflammatory factors with the hope that these would be reduced.
The trial design included a criteria used to determine if the trial was a success (or not) which is called a a ‘responder’ analysis. Initially the rate of MND progression of each person is measured using the ALS Functional Rating Scale-Revised (ALSFRS-R) over 6 month to give each person a quantified level of MND progression. If a person in the trial was to be classed as a ‘responder’ following the NurOwn treatment then their rate of ALSFRS-R would need to reduce by a minimum of 1.25 points per month i.e. their rate of physical decline due to MND slows down. It is then possible to count how many people ‘responded’ in the treatment group versus those in the placebo group.
Unfortunately, at the end of the 28-week study this comparison of responders between NurOwn and placebo was not statistically significant. 34.7% of people were responders in the NurOwn group i.e. met the responder definition described above compared to 27.7% in the placebo group.
Other measures that could indicate a successful treatment (known as Secondary endpoints) included safety, ALSFRS-R change from baseline, the Combined Assessments for Function and Survival (CAFS), slow vital capacity (SVC), and cerebrospinal fluid (CSF) biomarkers. ALSFRS-R mean scores were similar for both NurOwn and placebo groups and there was no difference in CAFS scores between the groups at the end of 28-weeks treatment. SVC was not different between the groups, although results may have been affected by the COVID-19 pandemic as SVC assessments were not possible at this time.
Further, it was reported that that NurOwn treatment resulted in an increase of neurotrophic biomarkers and reduction in neurodegenerative and neuroinflammatory biomarkers when compared to the placebo group, which is aligned with what the trial hoped to achieve. Follow up analysis will investigate whether these biomarker results, in addition to further analysis of the pre-specified subgroup of those with early disease, can reveal any additional information. You can read more about the trial here and the results here.
Brainstorm has used an Expanded Access Program (EAP) for participants less severely affected by MND, as measured by the ALSFRS-R, who completed the Phase 3 clinical trial. Eligible participants are now able to access a total of 9 doses. Data is continued to be collected in this EAP to better understand the potential benefits of longer term treatment. You can read more about the EAP here.
A correction to the data published in Muscle and Nerve in December 2021 was announced in August 2022. Analysis in the original publication used an incorrect model. This correction had an impact on one of the secondary endpoints, average change from baseline in ALSFRS-R, in the pre-specified subgroup of participants with a baseline score of at least 35. The data showed a statistically significant treatment difference of more than 2 points of those on NurOwn compared to those on placebo for that subgroup. You can read the correction here.
In August 2022, BrainStorm announced they were submitting a Biologics License Application (BLA) to the U.S. Food and Drug Agency (FDA) for the approval of Nurown for the treatment of MND.
The trial results showed that NurOwn did not show a statistically significant improvement compared to placebo. However, the study provided significant information about the study design and potential biomarkers of treatment response for use in future clinical trials. NurOwn did demonstrate the anticipated significant increase in neurotrophic factors, such as VEGF and decrease in neuroinflammatory markers like MCP-1, and a trend (not significantly significant) towards decrease in NfL .You can read more here.
Want to find out more about NurOwn? Check out the resources below:
Update on clinical trials - part 1
Virtual Symposium: Results from the Phase 3 clinical trial of NurOwn
Clinical Trials (Part 1) - Platform Presentations: Highlights from Perth
The Scientific Advisory Council (SAC) Briefing Notes
The Scientific Advisory Council for the International Alliance of ALS/MND societies consists of 9 members from USA, UK (including MND Association's Head of Research - Nick Cole), Sweden, Italy, South Africa, China, Australia and Canada.
They produce briefing notes as a trusted source of information about current experimental treatments in clinical development, such as NurOwn.
These notes are produced after many rounds of careful discussion between the SAC members.
You can find the briefing note for NurOwn here.