According to a recent BioSpace article from Heather McKenzie, the U.S. Food and Drug Administration’s Cellular, Tissue, and Gene Therapies Advisory Committee recently voted against approving NurOwn, an investigational therapy for people with amyotrophic lateral sclerosis (ALS), due to perceived issues with efficacy. This brings to a boiling point a multi-year saga during which BrainStorm Cell Therapeutics (“BrainStorm”), NurOwn’s developer, has worked to make the therapy available for those affected.
What is NurOwn?
The Motor Neurone Disease Association describes NurOwn as an investigational therapy that:
purifies mesenchymal stem cells from bone marrow extracted from the patient’s hip bone [and multiplies these cells] outside the body in combination with the NurOwn substance that make the cells produce neurotrophic factors. 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.
The Push Towards Approval
In 2021, BrainStorm announced that the company planned to file a Biologics License Application (BLA). A BLA is, essentially, a request for the FDA’s permission to begin delivering or introducing a biologic product into interstate commerce. The BLA also contains a variety of information including pre-clinical and clinical study data, product and manufacturing information, applicant information, and labeling.
However, the FDA strongly advised against submitting the BLA, noting that the data did not meet the need for substantial evidence of efficacy. After amending and correcting the data through a data analysis, BrainStorm filed the BLA in August 2022; three months later, it had been rejected. BrainStorm chose to file again anyway using the FDA’s “File Over Protect” protocol; this is described by the FDA as:
A request by an applicant to the Agency to file their application even though a refuse to file action on their application has been taken by the Agency.
Because of this, BrainStorm was granted a meeting with the Cellular, Tissue, and Gene Therapies Advisory Committee for this year. Prior to the meeting, the FDA issued a number of briefing documents that stated that BrainStorm lacked evidence of efficacy on NurOwn.
The Advisory Committee’s Rejection of NurOwn
In this most recent meeting, BrainStorm sought an approval for NurOwn in the indication of mild-to-moderate ALS. The company noted that this was the population it felt the therapy was best for given a subset analysis of the data. BrainStorm also offered post-hoc data from clinical studies which the company felt highlighted the therapy’s ability to improve clinical responses and certain biomarkers. However, the Advisory Committee still had a number of concerns.
First, the Advisory Committee noted that the drug, in the clinical studies, failed to meet primary and secondary endpoints. They felt that there was not enough data which suggested that NurOwn was effective in improving survival or reducing symptoms. In fact, survival was even worse for some treated populations in the Phase 3 study than in those receiving the placebo. As such, the Advisory Committee stated, while they felt like BrainStorm was working towards change, they felt that approving NurOwn did not make sense. Further, the Advisory Committee expressed concerns about statistical analyses and bias, issues with missing biomarker data, and the fact that there did not seem to be an association between biomarkers and clinical benefit. Says Andrew Buckley, a voting patient representative:
I didn’t find that [NurOwn] was effective. It seems to me like there’s more evidence to the contrary.
Altogether, 17 people voted against NurOwn. One voted in favor and one abstained. BrainStorm’s co-CEO felt disappointed that the company could not answer more questions and provide more information during the proceedings.
Looking to the future, the FDA will make a final decision on NurOwn by the PDUFA data of December 8, 2023. Although the FDA does not have to make decisions in-line with the Advisory Committee’s recommendations, these do often go hand-in-hand.
About Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that causes nerve cell death in the spinal cord, brain, and brain stem. As motor neurons die, the muscles weaken and waste away, causing a loss of voluntary movement. ALS is considered either sporadic or familial. While it affects people of all races and ethnicities, it is more common in white men over 60 years old. Symptoms vary significantly between those affected but may include:
- Frequent tripping/falling
- Difficulty performing everyday movements or small movements like holding objects
- Weakness in the arms, legs, and hands
- Progressive inability to move muscles throughout the entire body, which can lead to respiratory failure
- Slow or slurred speech
- Dysphagia (difficulty swallowing)
- Muscle cramping or twitching
