NurOwn for ALS

Last updated Nov. 1, 2024, by Marisa Wexler, MS
Fact-checked by Inês Martins, PhD

What is NurOwn for ALS?

NurOwn (debamestrocel) is an investigational cell-based therapy designed to slow disease progression and potentially extend survival in people with amyotrophic lateral sclerosis (ALS).

It’s being developed by Brainstorm Cell Therapeutics to be given as an intrathecal injection, or into the spinal canal.

Brainstorm submitted an application for NurOwn’s approval in 2023 over an objection from the U.S. Food and Drug Administration (FDA). But after experts nearly unanimously agreed that available data didn’t provide substantial evidence that NurOwn is effective for treating ALS, the company decided to withdraw its application. A Phase 3b trial is being planned to further assess NurOwn as a potential treatment for ALS.

Brainstorm is also testing NurOwn in multiple sclerosis clinical trials and is conducting preclinical studies in Parkinson’s disease.

Therapy snapshot

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 matured 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. Once inside the body, they are expected to secrete high levels of neurotrophic factors to improve motor neurons’ survival and potentially slow ALS progression.

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 3a trial, the therapy was given via three intrathecal injections eight weeks apart. In each injection, patients received about 4 mL of a suspension containing 125 million NurOwn cells. This is also the dosing regimen that will be tested in the upcoming Phase 3b trial.

Earlier trials also evaluated intramuscular NurOwn treatment, where the cells were injected into the muscles, either alone or 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 3a trial

Brainstorm’s unsuccessful request for FDA 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. Injections were given at weeks 0, 8, and 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.

Top-line 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.

After the trial ended, 10 patients opted to continue receiving NurOwn treatment as part of an expanded access program (NCT04681118). The program had two 28-week periods where treatment was given as in the main trial: three injections eight weeks apart with an additional 12 weeks of follow-up. There was a break in between each period.

Data presented in 2024 indicated that extended treatment with NurOwn led to continual decreases in markers of nerve damage and significant survival benefits compared with external controls.

Phase 3b trial

NurOwn is now planning a Phase 3b clinical trial, called BCT-006-US, to further test NurOwn as a potential ALS treatment. The trial is expected to enroll about 200 people, ages 18 to 75, with mild-to-moderate ALS and who first started experiencing symptoms less than two years before entering the study.

Participants in the study will receive three injections of NurOwn or a placebo, given every eight weeks over the course of 24 weeks, or about six months. Then, over a second six-month period, all participants will receive three injections of NurOwn also spaced by eight weeks. People on stable doses of standard ALS treatment will be allowed to continue receiving them.

The trial’s main goal is to see if NurOwn slows disease progression as measured by ALSFRS-R scores. Secondary measures will include changes in muscle strength and lung function, as well as survival and patient-reported outcomes.

Samples of blood and cerebrospinal fluid — the liquid that surrounds the brain and spinal cord — will also be collected to evaluate biomarkers of neuroinflammation, neurodegeneration, and neuroprotection.

The protocol and statistical analysis plan for the trial have been reviewed by the FDA under a Special Protocol Assessment. This ensures the trial’s design is generally adequate to support a future regulatory application.

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.

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