BrainStorm nets NurOwn ADCOM meeting over FDA objections

Developer utilized a 'file over protest' procedure as part of its application

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The U.S. Food and Drug Administration (FDA) will hold an advisory committee meeting to discuss BrainStorm Cell Therapeutics‘ application to approve NurOwn for amyotrophic lateral sclerosis (ALS).

Such a meeting, called an ADCOM, is normally for when a therapy is under regulatory review so experts can discuss its potential merits. The meeting is an independent review and the regulatory agency may or may not follow the committee’s recommendation.

While BrainStorm filed a biologics license application (BLA) in September for NurOwn’s approval, the FDA refused to review it due to insufficient evidence of its benefits.

With the BLA seemingly shut down, it wasn’t clear if an ADCOM would be scheduled. BrainStorm has utilized a “file over protest” procedure, however, meaning it will proceed with the application over the FDA’s objection, making an ADCOM attainable.

The application, which the company says has been amended to address most of the agency’s concerns, will be before the FDA’s Center for Biologics Evaluation and Research.

“The FDA provided us with more than one path to an ADCOM for NurOwn,” Chaim Lebovits, president and CEO of BrainStorm, said in a company press release. “Our goal has always been to make NurOwn available to people living with ALS as quickly as possible, therefore we chose the File Over Protest pathway since this offered the fastest path to an ADCOM and regulatory decision relative to other pathways provided by the FDA … we firmly believe our data support regulatory approval of NurOwn.”

The stem cell-based therapy was evaluated in a Phase 3 trial (NCT03280056) of 189 adults with rapidly progressing ALS, but it failed to meet its main efficacy goal of slowing disease progression relative to a placebo.

At that time, the FDA said there wasn’t enough data to support a regulatory application.

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Brainstorm: Efficacy results skewed by advanced disease patients

BrainStorm later argued the trial contained a large number of patients with advanced disease, which may have obscured NurOwn’s benefits.

These advanced patients often had some of the lowest possible scores on subscales of the ALS Functional Rating Scale-Revised (ALSFRS-R) when they enrolled, meaning there was no room to detect meaningful disease progression changes.

That assertion was supported by additional analyses that showed NurOwn could meaningfully and significantly slow disease progression when the severely affected participants were excluded.

With that data in hand, BrainStorm filed a new application, but the FDA declined to review it, citing a lack of “substantial evidence” of efficacy, in addition to concerns related to chemistry, manufacturing and quality control.

BrainStorm then requested a Type A meeting with the FDA, with a main goal of securing an ADCOM as quickly as possible. That meeting was held in January.

“Securing an ADCOM represents an important step towards our goal of making NurOwn broadly available to individuals living with ALS who are in urgent need of new, effective therapies,” said Stacy Lindborg, PhD, Brainstorm’s co-CEO.

The ADCOM meeting would serve as “an open forum for BrainStorm and the FDA, together with medical experts, statisticians, and the ALS community, to thoughtfully review all available evidence supporting NurOwn,” Lindborg said.

The FDA’s resistance to reviewing NurOwn was criticized by the ALS community, with two separate patient groups calling for an ADCOM within weeks of the FDA’s refusal to file.

“It is critical for all ALS treatments that they be given the chance to proceed to an ADCOM,” said Brian Wallach, a patient advocate and founder of nonprofit I AM ALS. “The ALS community has waited years for this ADCOM. 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.”

A date for the ADCOM has not been set.