BrainStorm Cell Therapeutics has been determined to get a twice-rejected amyotrophic lateral sclerosis treatment through the FDA process. And now, the dogged New York biotech will get another chance.
The FDA agreed to hold an advisory committee meeting after the company used an unusual regulatory Hail Mary. CEO Chaim Lebovits told investors on a Monday morning conference call that the advisory committee meeting will allow a public forum and open discussion of NurOwn, which the company has been pushing up hill ever since it failed a phase 3 trial in November 2020.
After the FDA rejected the application for NurOwn for the second time in November 2022, BrainStorm took the unusual step of pursuing a File Over Protest request. When the FDA issues a refusal to file letter after it receives an approval application, the sponsor can object, setting up a meeting to discuss what went wrong. If after that meeting the parties still disagree, a File Over Protest can be done. The FDA’s Center for Biologics Evaluation and Research will then review the application anyway.
BrainStorm has done just that, adding an amendment to the biologics license application that the biotech says responds to most of the FDA’s concerns, according to a Monday statement. The company's shares climbed 14% as the markets opened Monday, gaining 22 cents to $1.77.
The FDA flagged many issues. The agency originally rejected NurOwn in March 2021 via a rare public letter. At the time, the FDA stated that the data BrainStorm provided were "not at all statistically significant." But the agency acknowledged that ALS patients are desperate for options and promised to "use all expedited development and approval pathways" to get new therapies to patients as fast as possible.
BrainStorm's original application was based on a phase 3 trial that failed to show that NurOwn slowed disease progression compared with placebo. After shifting the analysis, BrainStorm vowed to forge on after receiving the initial rejection, claiming patients with less progressed disease had a reduced rate of disease progression.
BrainStorm rejigged the application with what it called “continued analysis” and feedback from scientific presentations of the phase 3 data, resubmitting it in August 2022. In November 2022, the FDA issued a refusal to file letter, which is when the agency determines that an application has significant deficiencies.
But BrainStorm said a couple different paths were left open to get NurOwn through the regulatory process. The File Over Protest was the fastest way to get the cell therapy before the advisory committee, Lebovits said Monday.
Co-CEO Stacy Lindborg, Ph.D., likened NurOwn’s journey to that of two ALS drugs that have made headway at the FDA despite questionable clinical data. The first was Amylyx’s Relyvrio, which finally secured an FDA nod in 2022. An advisory committee voted against recommending approval of the two-drug combo in March 2022 but then reconvened about six months later to consider a new analysis that the company submitted. That meeting ended with the committee recommending approval and the FDA agreed a few weeks later.
The second drug is Biogen and Ionis’ tofersen, which just got the advisory committee treatment last week. The expert panel ended in a split decision on the three questions. The committee agreed that a biomarker associated with ALS was reasonably likely to predict clinical benefit, but voted no on a question about whether the data supported the efficacy of tofersen. The committee also agreed that the benefit-risk profile was favorable based on available data.
“We see these recent developments as a major positive for individuals living with ALS, as they underscore a commitment amongst the community for regulatory flexibility when evaluating investigational therapies for this horrific disease,” Lindborg said during the call.
Lebovits said his company and the FDA have been working very closely to find a path forward for NurOwn. The parties met in January during a type A meeting, which ultimately led to the agreement that the advisory committee meeting would be scheduled. The FDA provided multiple options for getting NurOwn's application back on track, according to Lebovits.
BrainStorm’s efforts were supported by ALS patient advocacy groups, including I AM ALS, which was involved in the submission of a 30,000-signature petition to the FDA, lobbying for the agency to take up the application.
“The ALS community has waited years for this Ad Comm. It is time to let the science have a full, fair and transparent hearing so that we can get this treatment to people who are living with and dying from ALS as soon as possible,” said Brian Wallach, I AM ALS founder and patient advocate, in BrainStorm's statement.
The date of the advisory committee meeting was not stated, nor was the date that the FDA expects to ultimately rule on the application's approval. Lebovits said during the call that pulling together a meeting is a “huge undertaking,” but promised to communicate those dates when they are available.