BrainStorm’s New Trial May Support ALS Cell Therapy BLA

Chaim Lebovits

Credit: BrainStorm Cell

BrainStorm Cell Therapeutics has reached alignment with the FDA on chemistry, manufacturing, and control (CMC) aspects of a phase 3b clinical trial evaluating debemestrocel (Nurown) cell therapy for the potential treatment of amyotrophic lateral sclerosis (ALS).¹

"This in-person Type C meeting with the FDA was an important step as we finalize preparations for our pivotal Phase 3b trial of NurOwn. We are very pleased with the outcome and are now aligned with the FDA on resolving all previously outstanding CMC questions," Chaim Lebovits, President & Chief Executive Officer, BrainStorm, said in a statement.¹ "As with any cell therapy products, there are additional complexities in the manufacturing process, and it is important that we have alignment in advance with all the relevant groups within the FDA. We are committed to working closely with the FDA and to helping the ALS community, and are excited to move forward with the Phase 3b trial. Our ultimate goal is to achieve approval for NurOwn in order to address the unmet needs of patients."

The news comes a couple of months after the company announced that it had reached an accord with the FDA on a phase 3b trial design for debemestrocel, the endpoints of which would support a biologics license application (BLA) approval for the therapy. BrainStorm anticipates initiating the new phase 3b trial this year, following preliminary steps, including a review of the protocol with investigators, Institutional Review Board approvals of study sites, and engagement with the ALS patient community.²

"We have worked with leading neurologists, scientists, and members of the ALS community to create a robust study designed to evaluate the effectiveness and safety of NurOwn,” Stacy Lindborg, PhD, the co-CEO of BrainStorm Cell Therapeutics, added to the statement.² “This trial builds on valuable insights from our earlier studies and will enroll people living with ALS who are earlier in the course of their disease. Based on the evidence generated on NurOwn to date, we have a trial that we're optimistic will be positive. Over the past year, we've assembled an excellent team in clinical development that is highly qualified to execute this trial with excellence. We've been parallel processing to enable us to deliver the first dose in the trial in 2024, and we're anxious to get started."

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Debemestrocel is an investigational autologous mesenchymal stem cell (MSC) neurotrophic factor–secreting cell therapy product. The 2-part, multicenter BCT-006-US trial will enroll patients with early-stage ALS, with onset of symptoms within 24 months before enrollment. Furthermore, participants must have a score of at least 2 for all items on the Revised Amyotrophic Lateral Sclerosis Functional Rating (ALSFRS-R) and an upright slow vital capacity of at least 65% of what would be predicted for their gender, height, and age. Participants will be able to be take concomitant treatment with standard of care options while participating in the study.²

The first part of the study, lasting 24 weeks, will randomize approximately 200 participants to receive either NurOwn or placebo. NurOwn and the placebo will be administered via 3 intrathecal injections spaced 8 weeks apart from one another. The second part of the study has a similar protocol but will be carried out in an open-label fashion without a placebo group. Eligible participants from the first part of the clinical trial may choose to roll over into the second part.²

BCT-006-US's primary end point will be the change from baseline in ALSFRS-R score at 24 weeks posttreatment. Investigators will also analyze biomarkers for neuroinflammation, neurodegeneration, and neuroprotection.²

"We are pleased to have reached an agreement with the FDA on key elements of the phase 3b trial design that provides a potential path forward towards obtaining regulatory approval," Lebovits said in an earlier statement.² "We believe that having this SPA in place will help derisk certain regulatory aspects of the NurOwn clinical program. BrainStorm's ultimate goal is to provide a new treatment option that can help patients afflicted with ALS, and we believe that the SPA potentially brings us one step closer to this goal. We appreciate the Agency's engagement and guidance during the SPA process and look forward to moving forward with the study."

A previous phase 3 clinical trial (NCT03280056) tested debemestrocel against a placebo in patients with ALS, but that trial did not meet any of its primary or key secondary end points. Despite attempting to make a case for its efficacy with posthoc sensitivity analyses, BrainStorm ultimately pulled its original BLA for NurOwn in October 2023, before the FDA made a formal decision on the cell therapy.³

REFERENCES
1. BrainStorm Cell Therapeutics Reaches Alignment with FDA on CMC Aspects of Phase 3b NurOwn® Clinical Trial. News release. BrainStorm Cell Therapeutics. June 26, 2024. https://ir.brainstorm-cell.com/2024-06-26-BrainStorm-Cell-Therapeutics-Reaches-Alignment-with-FDA-on-CMC-Aspects-of-Phase-3b-NurOwn-R-Clinical-Trial
2. BrainStorm cell therapeutics announces agreement with FDA on a special protocol assessment (SPA) for phase 3b trial in ALS. News release. April 9, 2024. Accessed April 9, 2024. https://ir.brainstorm-cell.com/2024-04-09-BrainStorm-Cell-Therapeutics-Announces-Agreement-with-FDA-on-a-Special-Protocol-Assessment-SPA-for-Phase-3b-Trial-in-ALS
3. BrainStorm Cell therapeutics to meet with US FDA to discuss development plan for NurOwn as a treatment of ALS. News release. BrainStormCell Therapeutics Inc. October 18, 2023. Accessed December 21, 2023. https://ir.brainstorm-cell.com/2023-10-18-BrainStorm-Cell-Therapeutics-to-Meet-with-US-FDA-to-Discuss-Development-Plan-for-NurOwn-as-a-Treatment-of-ALS