BrainStorm making cuts to support new trial, advance NurOwn for ALS
Planned Phase 3b trial in US a focus of future meeting with FDA
The decision follows the recent withdrawal of its regulatory application with the U.S. Food and Drug Administration (FDA) seeking the therapy’s approval, after an FDA advisory committee overwhelmingly decided that available data from a Phase 3 clinical trial (NCT03280056) were insufficient to support NurOwn’s efficacy in ALS.
The FDA since has offered a face-to-face meeting with company officials, and BrainStorm is continuing to collect NurOwn data to support a future regulatory application. This includes additional biomarker and long-term safety and survival data from the completed Phase 3 trial, as well as a planned Phase 3b trial in the U.S. with an open-label extension.
That new clinical study, a focus of the upcoming FDA meeting, likely will be in ALS patients with less advanced disease.
‘Steadfast in our goal to make NurOwn available to the ALS community’
To support these goals, BrainStorm is exploring options for raising capital and will reduce and refocus existing resources. These efforts include a targeted, roughly 30% reduction in its workforce, with employees crucial for the new clinical trial and future regulatory submissions being retained, it announced in a company press release.
NurOwn’s executive vice president and chief medical officer — reported to be largely in charge of global medical affairs and broader launch activities — is among those stepping down. Overall, the company expects to cut by half the company’s total resource consumption.
“We remain steadfast in our goal to make NurOwn available to the ALS community as quickly as possible, and we believe that this strategic realignment offers our best chance for success,” said Chaim Lebovits, president and CEO of NurOwn. “While remaining open to partnership opportunities that could accelerate growth, the steps we are taking now reflect our unwavering commitment to those battling this horrific disease and our firm belief in the potential value of NurOwn.”
BrainStorm also is consulting with principal investigators from its NurOwn trials, independent ALS experts, and a patient advisory group to prepare the Phase 3b trial’s design and for the upcoming FDA meeting.
A cell-based therapy, NurOwn involves collecting a person’s stem cells and engineering them in the lab to produce high amounts of a signaling molecule thought to promote nerve cell health and growth. When returned to the patient via an injection directly into the spine, the therapy is expected to support nerve cell survival.
The completed Phase 3 trial, which enrolled 189 people with rapidly progressing ALS, failed to meet its main goal of demonstrating NurOwn was superior to a placebo at slowing disease progression. This was assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R), in which lower scores indicate greater disability.
Clinically meaningful responses to NurOwn, however, were seen in a pre-specified group of patients with less-advanced disease, but they did not differ significantly from those of patients given a placebo.
But Brainstorm used a ‘filed over protest’ procedure to move its application ahead, allowing for the Sept. 27 advisory committee meeting that, in a 17-1 vote, found insufficient support.
Possibility of a floor effect masking benefits in earlier Phase 3 trial
The company has argued that further analyses of NurOwn data indicate the presence of a floor effect in the ALSFRS-R, the scale used to measure progression in its Phase 3 trial. Given that a large number of participants had advanced disease and some of the lowest possible scores on that measure’s subscales, there was no room for further meaningful score declines, even if patients — including those in the placebo group — were continuing to lose functionality.
As such, it’s possible that meaningful and significant differences between NurOwn’s use and a placebo were missed. This hypothesis is supported by the therapy being shown to slow disease progression in trial patients with less severe disease, where the impact of the floor effect isn’t expected to be as profound.
“While the Phase 3 trial was confounded by the ALSFRS-R scale’s inability to measure disease progression in participants with advanced ALS, the trial did demonstrate a clinically meaningful response in a pre-specified subgroup of patients with less advanced disease,” said Stacy Lindborg, PhD, co-CEO of BrainStorm. “This finding was further supported by biomarker data.”
The FDA responded by questioning the presence of this floor effect and repeating its chief efficacy concerns shortly before the advisory committee meeting.
“Based on learnings from the Phase 3 trial, we believe in the utility of NurOwn in mild to moderate ALS and that the ALS community deserves every effort we can give to definitively demonstrate its clinical value,” Lindborg said.