NurOwn (debamestrocel) for ALS
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What is NurOwn for ALS?
NurOwn (debamestrocel) is an investigational cell-based therapy being tested in clinical trials as a treatment for amyotrophic lateral sclerosis (ALS).
BrainStorm Cell Therapeutics announced plans in 2022 to submit an application to the U.S. Food and Drug Administration (FDA) for NurOwn’s approval. The agency declined to review the application on the basis that available clinical trial data were not sufficient to support its approval, however.
BrainStorm decided to proceed with the application over the FDA’s objection to secure an advisory committee meeting, where independent experts will discuss the therapy’s potential benefits. The meeting will take place Sept. 27 and a final decision is expected by Dec. 8.
BrainStorm is also testing NurOwn in multiple sclerosis clinical trials and is conducting preclinical studies in Huntington’s disease, Parkinson’s disease, and autism spectrum disorder.
Therapy Snapshot
| Treatment Name: | NurOwn |
| Administration: | Being tested in ALS as an intrathecal (into-the-spinal-canal) injection |
| Clinical testing: | Completed a Phase 3 clinical trial in ALS |
How does NurOwn work in ALS?
ALS is a progressive neurodegenerative disease wherein motor neurons — the nerve cells that control muscle movement — become progressively dysfunctional and die, resulting in a gradual decline in muscle function and strength.
NurOwn is a cell-based therapy that’s designed to counteract the neurodegeneration process and help nerve cells survive.
It uses a patient’s own mesenchymal stem cells (MSCs), which are precursor cells that can differentiate into various cell types. After being isolated from a patient’s bone marrow, MSCs are grown in the lab and converted into cells that produce a large amount of neurotrophic factors — signaling molecules known to promote nerve cell growth and survival.
These mature cells are then returned to the patient through an injection directly into the spinal canal, where they should secrete high levels of neurotrophic factors to improve motor neurons’ survival.
How will NurOwn be administered in ALS?
The first step in treatment with NurOwn is to collect a patient’s MSCs. In clinical trials, this has been done via bone marrow aspiration, where a large needle is used to collect a bone marrow sample from the hip bone.
After the MSCs are collected, they are modified in a laboratory for about two weeks before being administered. In a Phase 3 trial, the therapy was given via three intrathecal injections, that is, into the spinal canal, at two-month intervals. In each injection, patients received about 4 mL of a suspension containing 126 million NurOwn cells.
Earlier trials also evaluated intramuscular NurOwn treatment, where the cells were injected into the muscles, either alone or with with intrathecal injections.
NurOwn in ALS clinical trials
NurOwn was first explored in a Phase 1/2 trial (NCT01051882) in 12 patients and a Phase 2a trial (NCT01777646) in 14 patients, both of which took place in Israel. Their primary aim was to evaluate the safety of the cell treatment, administered as a single dose either intrathecally or via an injection into the muscle.
Results from both trials demonstrated the therapy was generally well tolerated, with most side effects being mild and temporary. No treatment-related serious side effects were reported in either trial.
The intrathecal administration showed signs of slowing disease progression, but not the intramuscular one. There were trends toward a slower decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, which measure patients’ ability to carry out daily living activities, and a significant slowing in lung function decline, as measured through the forced vital capacity (FVC) parameter.
Phase 2a trial
A second Phase 2a study (NCT02017912) enrolled 48 people with ALS whose symptoms started one to two years before screening. Participants were followed for three months to establish initial rates of disease progression and then were randomly assigned to a single dose of NurOwn or a placebo.
Treatment was given via combined intramuscular and intrathecal injections containing a total of 173 million cells. Participants were followed for six months after the injections.
The study met its main goal of demonstrating that treatment was safe. Serious side effects were reported by 25% of patients in the NurOwn group and 17% of those given a placebo, but none were related to treatment and no patients died during the study.
Results also showed that functional decline, as assessed by changes in ALSFRS-R scores, tended to be reduced with NurOwn in the first month of treatment, but no changes between the NurOwn and placebo groups were observed after two months.
The treatment was particularly more effective in a group of patients with rapidly progressing disease — defined as a decline of more than two ALSFRS-R points during the three-month pretreatment period.
In these patients, NurOwn significantly slowed disease progression compared with a placebo in the first month and showed a trend toward functional improvement (an increase in ALSFRS-R scores) at all assessments.
NurOwn also reduced several markers of inflammation and neurodegeneration in the spinal fluid, but failed to slow the decline in lung function and muscle strength in both the whole group and in the fast progressing patients.
Phase 3 trial
BrainStorm’s request for the approval of NurOwn was based on data from the BCT-002 Phase 3 clinical trial (NCT03280056), which enrolled 189 ALS patients, ages 18-60, who had experienced a first ALS symptom, including limb weakness, up to two years before screening and had rapidly progressing disease.
The participants were randomly assigned to three intrathecal doses of NurOwn or a placebo, each given two months apart and containing 125 million cells — the highest dose that had been safely administered intrathecally in previous clinical trials. The last injection was given at week 16 and patients were monitored for 28 weeks (about seven months).
All could continue to receive standard treatment with riluzole-based medications, but not Radicava (edaravone).
The study’s main goal was to determine the treatment’s effect on disease progression, as measured by the proportion of patients showing at least a 1.25-point slower monthly decline in ALSFRS-R scores over the 28 weeks compared with the three months before treatment initiation.
Topline results showed the trial failed to meet that goal. While more patients on NurOwn than in the placebo group had a slower disease progression (32.6% vs. 27.7%), the difference didn’t reach statistical significance. The mean change in ALSFRS-R scores, lung function decline, and a combined assessment of function and survival also were not significantly different between the groups.
One possible reason for the trial’s lack of significant effect, according to BrainStorm, was that many patients had relatively advanced disease when the study started. As some patients already had the lowest possible scores in some subscales of the ALSFRS-R, that creates a “floor effect” that prevents changes in disease progression from being properly detected.
In a prespecified analysis of patients with less advanced disease — those with an initial ALSFRS-R score of at least 35 — there was an even greater difference between NurOwn and placebo responders (34.6% vs. 15.6%). The findings were deemed clinically meaningful and statistically significant.
In several post hoc analyses — designed and carried out after the study was complete and all data had been collected — researchers examined NurOwn’s clinical benefits after excluding patients with lower ALSFRS-R scores or with signs of a floor effect on multiple ALSFRS-R subscales. In most of these analyses, there was a significant slowing of functional decline in patients given NurOwn over those on a placebo. Furthermore, a reduction in biomarkers associated with nerve cell damage was seen in patients on NurOwn.
Common side effects of NurOwn
The most common side effects of NurOwn reported in ALS clinical trials include:
- headache
- back pain
- fever
- vomiting
- pain in the neck, legs, and extremities
- joint and muscle pain
- bruising at the injection site.
ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about NurOwn
NurOwn is an experimental cell-based therapy that is being investigated in clinical trials as a potential treatment for amyotrophic lateral sclerosis (ALS). It contains specialized stem cells that produce significant amounts of molecules known to promote nerve cell growth and survival. This is expected to reduce nerve cell damage and potentially slow disease progression in ALS patients.
BrainStorm Cell Therapeutics, the company developing NurOwn, has asked the U.S. Food and Drug Administration (FDA) to approve the therapy. The agency initially declined to review the application, but the company proceed with the filing to secure an advisory committee meeting, where independent experts will discuss the therapy’s potential benefits. The meeting will take place in September and a final regulatory decision is expected by December.
The most common side effects of NurOwn reported in amyotrophic lateral sclerosis (ALS) clinical trials include headache, pain, fever, vomiting, and bruising at the injection site. Still, because patients react differently to a given medication, not everyone will experience similar side effects related to NurOwn treatment. Patients should talk with their care team to better understand how the medication may affect them.
The interaction between alcohol and NurOwn has not been well studied. Patients should speak with their healthcare team to know if and how much alcohol is safe to drink on this therapy.
In the BCT-002 Phase 3 trial, which supported BrainStorm’s application to approve NurOwn, there were signs of a significant slowing in disease progression in people with less advanced disease after seven months. Because amyotrophic lateral sclerosis (ALS) has a variable disease course, some patients may see benefits earlier than others, however. It’s recommended that patients talk with their healthcare provider to better understand when an effect may become evident.
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