FDA clears Phase 3b trial of NurOwn for ALS
Trial to recruit about 200 patients with moderate disease
The U.S. Food and Drug Administration (FDA) has cleared a Phase 3b clinical trial to test Brainstorm Cell Therapeutics’ cell-based therapy NurOwn (debamestrocel) in people with amyotrophic lateral sclerosis (ALS).
The trial, ENDURANCE (NCT06973629), is expected to open soon at more than a dozen sites across the U.S. It plans to recruit about 200 adults with moderate disease who have been experiencing symptoms of ALS, including muscle weakness, for less than two years.
The trial’s protocol has been reviewed and agreed to by the FDA under a special protocol assessment. That means the FDA has looked at how the study is designed, including what it aims to measure and how the data will be analyzed, and confirmed it’s suitable to support a future application for potential approval of NurOwn.
“This FDA clearance is a defining milestone for BrainStorm and the ALS community,” Chaim Lebovits, Brainstorm’s president and CEO, said in a company press release. “We are now positioned to swiftly activate clinical sites in a phased manner, diligently preparing to enroll the first patient in the Phase 3b trial.”
Collecting stem cells from patients
NurOwn uses a patient’s own mesenchymal stem cells (MSCs), which are stem cells that can differentiate into various cell types and also produce factors important for neuronal health, called neurotrophic factors.
The cells are collected from a patient’s bone barrow and grown in the lab to several millions. They are given cues to turn into cells that produce large numbers of neurotrophic factors, boosting their ability to promote nerve cell growth and survival once infused back into the patient.
By counteracting the neurodegeneration process, the therapy is expected to slow disease progression and potentially extend survival in people with ALS.
In a Phase 3 clinical trial (NCT03280056) involving 189 adults with rapidly progressing ALS, NurOwn failed to significantly slow disease progression compared with a placebo. But patients with less advanced disease appeared to benefit from the treatment.
While the FDA determined that data from the trial were insufficient to support an application for approval, the company decided to proceed with the application over the regulators’ objections.
The company believed that a floor effect on ALS Functional Rating Scale-Revised (ALFRS-R) scores — where patients’ scores were already so low that further declines in the placebo group could not be detected — had affected the results. An FDA advisory committee questioned this hypothesis and confirmed that the findings still didn’t provide enough evidence of NurOwn’s benefits, leading the company to withdraw its application.
Since then, Brainstorm has been working with the FDA on the protocol for the now-cleared ENDURANCE trial, which is expected to provide enough data to allow a resubmission of an application with the FDA.
As part of the trial, patients will be randomly assigned to receive either NurOwn or a placebo as an injection into the spinal canal every eight weeks for 24 weeks (about six months). They will then have the option to enter an open-label extension, during which all will receive NurOwn every eight weeks for an additional six months.
The trial’s main goals are to test how safe and well tolerated NurOwn is compared with a placebo, and how effectively it slows disease progression, as measured with ALSFRS-R, over the first 24 weeks of treatment. Additional outcomes, such as lung function, muscle strength, quality of life, and changes in disease biomarkers, will also be assessed.
“We are actively working to secure funding … to ensure the timely and successful launch of [the ENDURANCE trial],” Lebovits said.
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