BrainStorm's ALS cell therapy resoundingly rejected by FDA advisers

 FDA advisers were unmistakable in their assessment of BrainStorm Cell Therapeutics’ treatment for amyotrophic lateral sclerosis (ALS): there's just no evidence it works.

Members of the Cellular, Tissue, and Gene Therapies Advisory Committee voted 17 to 1—with one abstention—that there was not substantial evidence to show that the company’s cell therapy, NurOwn, was effective at stymying the progression of mild-to-moderate ALS. It’s a near-final blow for the company’s approval ambitions after two prior rejections from the agency. 

The decision validates what the agency has conveyed for more than two years now, which is that NurOwn has failed to show any evidence of efficacy and that critical parts of the manufacturing process remain unclear.

The agency posted a rare regulatory update in March 2021 acknowledging the need for new ALS treatments but underscored the lack of benefit in the company’s phase 3 trial. The FDA also flagged “a modest excess in deaths in those treated with NurOwn,” though the significance was unclear at the time. FDA said then that if BrainStorm had additional clinical studies planned, then it would continue to provide advice and guidance.

That didn’t happen and BrainStorm instead submitted an approval application in 2022 based on an exploratory analysis of the same phase 3 trial. The FDA refused to accept the application for a host of reasons that centered on a lack of demonstrated efficacy and insufficient manufacturing information. The agency told the company to try again with more data but BrainStorm instead filed the application over protest in February—a rarely used Hail Mary drugmakers can leverage to force a public hearing on an application. 

Just a few days ago, BrainStorm made a last-minute change to the application to trim the desired indication from patients with ALS to patients with mild-to-moderate ALS. The FDA held firm during the meeting that the data do not suggest that the treatment benefits patients in this newly selected subset, either. 

At the meeting, BrainStorm emphasized two key points to try and make the case for efficacy: the first was that a subgroup of patients with a Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) of 35 or higher had a much better response to the treatment than placebo.

This scale ranges from 0 to 48 and measures the severity of the disease. A high score indicates more normal function, while lower scores suggest more severe progression.

The rate of response for patients with scores below 35, or more severe disease, was about the same as placebo, the company said.

https://www.fiercebiotech.com/biotech/brainstorm-cells-als-cell-therapy-resoundingly-rejected-fda-experts