NurOwn

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 FDA declined to consider the approval but have now agreed to hold a Advisory Committee Meeting for NurOwn through the FDA's File over Protest route. The meeting will be held on the 27th September, with a final decision to made by 8 December 2023.

October 2023 - BrainStorm have announced they are withdrawing the Biologics License Application for NurOwn in the United States. BrainStorm are now discussing the path forward with the Food and Drug Administration (FDA), including the development of a protocol for an additional clinical trial. You can read more here. 

September 2023 - The Food and Drug Administration (FDA) Advisory Committee voted against the approval of NurOwn in the United States. Overall, when asked the question “Does the data presented demonstrate substantial evidence of effectiveness for the treatment of mild to moderate ALS?” the panel answered no. You can read more here.

July 2023 - Additional biomarker data was released. You can read more here. 

June 2023 - The Food and Drug Administration (FDA) Advisory Committee meeting which will provide recommendations for the approval of NurOwn has been set for 27 September 2023. Recommendations from this Committee are non-binding. The final decision regarding the approval of NurOwn in the US will be made by 8 December 2023. You can read more here. 

March 2023 - BrainStorm Cell Therapeutics have announced that the Food and Drug Administration (FDA) will hold an Advisory Committee Meeting for the approval of NurOwn. You can read more here.

Dec 2022 - BrainStorm Cell Therapeutics announced that the Food and Drug Administration (FDA) granted a Type A meeting to discuss the contents of the refusal to file letter received in Nov 2022. You can read more here. 

Dec 2022 - BrainStorm Cell Therapeutics have announced that they have submitted a Type A meeting request to the U.S. Food and Drug Administration (FDA). You can read more here. 

Nov 2022 - BrainStorm Cell Therapeutics have announced that they have received a refusal to file letter from the Food and Drug Administration (FDA) in the United States for the New Biologics License Application (BLA) for NurOwn as a treatment of ALS. You can read more here. 

Aug 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. 

• 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