BrainStorm Reaches Agreement with FDA on Special Protocol Assessment for ALS Trial

Rare Daily Staff

BrainStorm Cell Therapeutics said it has reached an agreement with the U.S. Food and Drug Administration on the design of a phase 3b study of its experimental NurOwn therapy in patients with amyotrophic lateral sclerosis under a Special Protocol Assessment.

The Special Protocol Assessment (SPA) agreement with the FDA validates the clinical trial protocol and statistical analysis of the planned phase 3b trial of NurOwn, demonstrating their adequacy for addressing objectives that support an application for approval to market the therapy as a treatment for amyotrophic lateral sclerosis (ALS). An SPA is a process in which drug developers may ask to meet with the FDA to reach an agreement on the design and size of certain clinical trials to determine if they adequately address scientific and regulatory requirements for a study that could support marketing approval.

Chaim Lebovits, president and CEO of BrainStorm, said the agreement “provides a potential path forward towards obtaining regulatory approval” and that it will “help de-risk certain regulatory aspects of the NurOwn clinical program.”

Brainstorm has faced a string of setbacks in seeking approval for NurOwn in ALS. In March 2021, the agency told the company that a review of its data indicated that it did not have adequate clinical data to seek an approval. It did file for approval in 2022 following additional analysis of its phase 3 data, but the FDA refused to review the application. Brainstorm withdrew the application nearly a year later.

The company said it anticipates starting the phase 3b study in 2024, after reviewing the protocol with investigators, securing study site Institutional Review Board approvals, and engaging with appropriate members of the ALS community.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death. More than 90 percent of people with ALS have sporadic disease, showing no clear family history. ALS affects approximately 29,000 people in the U.S.

Brainstorm’s NurOwn technology platform targets disease pathways with MSC-NTF cells that are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells are designed to effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression.

The phase 3b trial will be a two-part, multicenter, study designed to assess the efficacy and safety of NurOwn in patients with ALS. The entry criteria will enroll participants earlier in the course of their disease. Patients will also be allowed to receive concomitant treatment of an approved standard of care.

Part-A is a double blind, placebo-controlled period of 24 weeks duration. Up to approximately 200 patients are planned to be enrolled and randomized 1:1 to NurOwn or placebo treatment groups. There will be a screening period of six to nine weeks, during which eligible participants will undergo a single bone marrow aspiration procedure to procure the mesenchymal stem cells (MSCs) that will be used to manufacture each participant’s NurOwn treatment for the duration of the trial. Patients will then be randomized 1:1 and treated with NurOwn or placebo via three repeated intrathecal injections, once every eight weeks. All eligible patients who complete Part-A will have the option of entering Part-B, an open-label extension period of 24 weeks duration, where all participants will receive three repeated intrathecal injections of NurOwn, once every eight weeks.

The primary efficacy endpoint is the change in the Revised Amyotrophic Lateral Sclerosis Functional Rating (ALSFRS-R) total score from baseline to Week 24. Primary inference from the trial will be based on a p-value from the combined assessment of function and survival to account for mortality observed in the trial. Cerebrospinal fluid and blood samples will be collected for analysis of biomarkers of neuroinflammation, neurodegeneration, and neuroprotection. An independent Data Monitoring Committee will monitor the safety of the trial participants.

Photo: Chaim Lebovits, president and CEO of BrainStorm