The FDA has carried on a year-long disagreement with BrainStorm Cell Therapies, the developer of the experimental stem cell treatment called NurOwn. It is referred to as a personalized cell treatment.
According to an article in BioPharmaDive, a hearing for the public is expected at a later date. At issue is the evidence needed to approve a drug that can effectively treat ALS.
BrainStorm recently announced that the FDA will conduct a panel consisting of experts who will review BrainStorm’s experimental medicine. As of this writing the meeting has not been scheduled. It evolved from the unusual step taken by BrainStorm in which the company requests the filing of its application for approval despite protest by the FDA.
Ten Years and Limited Success
The filing of an application despite the FDA’s protest is a formal process made available after a drugmaker receives a “refuse-to-file” letter which includes reasons why the FDA judged the submission as incomplete.
The procedure does not have an encouraging track record with only four filings in ten years and none had been approved.
In November 2022 the FDA regulators did not review BrainStorm’s application citing NurOwn’s trial which did not meet its primary endpoint.
BrainStorm argued that the design of the clinician trial and the type of participants had a negative effect on the drug’s performance. The company now refers to recent analyses that support its arguments.
In a recent interview, Stacy Lindborg, BrainStorm’s CEO, stated that the company feels that they have a strong case and are working diligently to prepare for the meeting to be held by the Advisory Committee.
Lindborg offered an alternative plan would have been to resubmit the application but that would entail lengthy delays along the regulatory path.
Whereas the filing ‘over protest’ represented the shortest amount of time to achieve results.
Support from the Community
BrainStorm has received support from the ALS community backing its ‘filing over protest’. The community’s petition is supported by twenty advocacy groups with signatures of over thirty thousand people calling for the FDA to conduct an advisory committee meeting for NurOwn.
According to Lindborg, several FDA approvals indicate the FDA’s flexibility. Amylyx Pharmaceutial’s ALS drug Relyvrio was approved in 2022. In addition, the FDA agreed to assess Biogen’s experimental treatment tofersen in spite of its study that had failed.
The committee that will evaluate NurOwn reviewed tofersen last week ending with a favorable 9 to 0 vote. All participants agreed that there was a reasonable likelihood that tofersen’s effect on the protein associated with nerve damage has the potential of producing clinical benefits.
However, the same did not hold true in the second vote. The committee was not convinced that Biogen’s data showed tofersen’s effectiveness. In this instance, a favorable vote could persuade the FDA’s issuance of a conditional clearance on April 25th, the ‘date of decision’.
Yet despite its optimism, BrainStorm may be in for a rough session as the FDA was not impressed with the company’s data. The Agency stated that at the time of application, there was little data in support of the proposed therapy’s clinical benefit.
About Phase III
The data in question was generated by a Phase III clinical trial consisting of 189 ALS patients who randomly received a placebo or NurOwn. That phase of the trial lasted twenty-eight weeks resulting in approximately 33% of participants treated with NurOwn meeting the criteria versus 28% responding after treatment with a placebo.
Unfortunately, the minimal difference in response lacked significance according to an FDA statement in March of 2021.
Although BrainStorm readily acknowledges that the study did not meet its intended goal, the company references additional analyses showing that participants with a lesser degree of ALS reacted better with NurOwn than with the placebo.
BrainStorm further argued that as several participants were burdened with severe functional impairments, it was difficult to determine if the treatment slowed their decline. Lindborg defended this position by adding that a patient’s decline cannot be measured under these circumstances.
At this juncture, the FDA’s opinions of the latest arguments remain unknown. Also, the FDA does not usually divulge ‘refuse-to-file’ letters to the public. Therefore, these matters are left to the company involved in the dispute.