FDA Agrees in Advance to Trial Framework as NurOwn Plans New 200-Patient Phase 3 Study in ALS

Amyotrophic lateral sclerosis (ALS) progresses rapidly, yet late-stage trials often struggle to clearly identify treatment effects because of differences in patients’ disease course and the measurement limitations of functional scales. BrainStorm Cell Therapeutics is preparing a new late-stage Phase 3 study of its autologous cell therapy NurOwn, seeking to move treatment earlier and use more focused patient criteria to reassess whether it can slow functional decline.

The Phase 3b trial, named ENDURANCE, is expected to enroll approximately 200 adults, who will initially be assigned 1:1 to NurOwn or placebo. The first 24 weeks will be a randomized, placebo-controlled phase, followed by a 24-week open-label extension in which all participants will receive NurOwn every eight weeks to continue collecting data on safety and the duration of treatment effects.

The study will target patients whose symptoms began no more than 24 months earlier and who retain a certain level of respiratory and daily functioning. The primary efficacy endpoint is the change from baseline in the total score on the revised ALS Functional Rating Scale (ALSFRS-R) at Week 24. The FDA-agreed analytical framework also includes an assessment method combining functional and survival status, with the aim of reducing interference in the interpretation of results caused by death or study withdrawal.

The clinical trial registry lists ENDURANCE as a quadruple-blind study covering participants, care providers, investigators, and outcome assessors, while company documents describe the controlled phase more broadly as double-blind. Both point to the same core design: minimizing treatment expectations and assessment bias as much as possible before unblinding. The registry lists 15 study sites in the United States, but the record was last verified in May 2025. The UCSF page, as of the status shown, still lists the study as not yet recruiting and estimates completion in May 2029.

NurOwn is also known as debamestrocel or MSC-NTF. The manufacturing process uses patients’ own bone marrow-derived mesenchymal stem cells, which are induced outside the body to become cells capable of secreting neurotrophic factors and immunomodulatory signals before being infused back into the patient. The approach is intended to act on both neuroprotection and the inflammatory environment, but mechanistic plausibility does not equal clinical benefit. ENDURANCE must still demonstrate an effect using its prespecified functional endpoint.

The FDA’s Special Protocol Assessment (SPA) is an important regulatory foundation for this development program. It means the FDA has agreed in writing to key elements of the trial design and statistical analysis, reducing the risk that the primary design will be deemed unacceptable only after the study is completed. However, an SPA is not an endorsement of efficacy and does not guarantee that the trial will succeed or that NurOwn will ultimately be approved. BrainStorm has said that, if the 24-week controlled phase is successfully completed, the resulting data may support resubmission of a biologics license application.

The most immediate constraint is execution capacity. Information previously submitted by BrainStorm to U.S. securities regulators showed that, as of the end of March 2026, cash, cash equivalents, and restricted cash totaled approximately $200,000; the company recorded a net loss of approximately $2.1 million for the same quarter and had current liabilities of approximately $11.8 million. The company has also explicitly stated that enrollment depends on securing the necessary financing. These figures do not represent its real-time cash position in August, but they show that even if study centers and manufacturing operations are ready, fundraising may still determine when the trial actually begins.

Background

ALS drug development is advancing along multiple paths. NurOwn seeks to use patients’ autologous cells to provide multiple neurotrophic signals, while antisense oligonucleotide therapies are targeting RNA-regulatory pathways such as UNC13A. The two approaches reflect that ALS is not a disease caused by a single mechanism and also underscore that late-stage studies must simultaneously address patient stratification, the sensitivity of functional scales, and sustainable manufacturing. For NurOwn, the next materially significant milestone is not another announcement of a trial blueprint, but securing funding, formally beginning enrollment, and completing the 24-week controlled data collection.