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<a href="https://brainstorm-cell.com">BrainStorm Cell Therapeutics</a> has had a meeting with the U.S. Food and Drug Administration (FDA) seeking an agreement on its plans for a confirmatory Phase 3b trial of <a href="https://alsnewstoday.com/nurown/">NurOwn</a>, a cell-based treatment the company is developing for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The main goal of the meeting, <a href="https://alsnewstoday.com/news/brainstorm-fda-meeting-dec-6-plans-nurown-als-trial/">announced</a> by BrainStorm in late November, was to discuss a special protocol assessment, or SPA, which ultimately ensures that the design of an upcoming trial is in line with FDA requirements to support a future marketing application.
The company now will submit the needed documents, as defined by the regulatory agency during the meeting, to support the SPA.
“Our meeting with the FDA provided us with valuable input on the Phase 3b trial design, outlining clear steps forward,” Chaim Lebovits, BrainStorm’s president and CEO, said in a <a href="https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-announces-outcome-of-fda-meeting-on-nurown-in-als-302008950.html">company press release</a>.
While the SPA does not guarantee that the trial results will be enough to support a potential approval, it “will serve to help de-risk certain regulatory aspects of the NurOwn clinical program,” Lebovits said.
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<h3>BrainStorm aims to resubmit NurOwn application with new trial data</h3>
The meeting was held a couple of months after BrainStorm <a href="https://alsnewstoday.com/news/brainstorm-drops-application-nurown-als-regroup/">withdrew its application</a> for NurOwn’s approval in the U.S. following a negative opinion by an FDA advisory committee. According to that committee&#8217;s overall findings, there was not enough evidence of the therapy’s efficacy. The negative opinion came just three months before the FDA had been expected to issue a decision on NurOwn&#8217;s approval.
BrainStorm then sought the face-to-face meeting with an aim toward ultimately getting its therapy approved.
“We recognize the urgency in providing ALS patients with safe and efficacious treatments and are committed to agreeing on a regulatory path forward for NurOwn. We are grateful for the FDA’s continued support and guidance and look forward to providing further updates once we have more clarity on an SPA,” Lebovits said.
[quote=&#8221;center&#8221;]We recognize the urgency in providing ALS patients with safe and efficacious treatments and are committed to agreeing on a regulatory path forward for NurOwn.[/quote]
In ALS, motor neurons — the nerve cells that control voluntary movements of muscles — become damaged and die. As a result, people with ALS experience <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a> such as muscle twitching, wasting, and weakness, which worsen over time.
NurOwn involves collecting mesenchymal stem cells from a patient’s bone marrow. These stem cells, which can give rise to a variety of cell types, are matured in the lab into cells that produce large amounts of molecules that could help motor neurons survive.
The lab-grown cells are then returned to the patient through injections into the spinal canal, where they are expected to release the beneficial molecules and prevent motor neurons from dying, thereby slowing disease progression.
BrainStorm’s initial application for NurOwn’s approval was mainly based on data from a <a href="https://clinicaltrials.gov/study/NCT03280056">Phase 3 trial (NCT03280056)</a> that enrolled 189 adults with a <a href="https://alsnewstoday.com/als-diagnosis/">diagnosis of ALS</a> and rapidly progressing disease. Participants were given three injections of either NurOwn or a placebo at two-month intervals.
While a greater proportion of NurOwn-treated patients had a slower disease progression, as measured by a 1.25-point slower rate of decline in the ALS Functional Rating Scale (ALSFRS-R) after about seven months, the difference <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">did not reach statistical significance</a>.
With a Phase 3 trial that failed to meet its main goal, and despite <a href="https://alsnewstoday.com/news/nurown-benefits-patients-less-severe-als-analyses-show/">promising results</a> in trial participants with less advanced disease, the FDA <a href="https://alsnewstoday.com/news/fda-declines-considering-nurown-als/">declined to review</a> an application for NurOwn’s approval, citing insufficient clinical evidence for its efficacy. The advisory committee meeting then backed the agency’s opinion.
The company now hopes that the future Phase 3b trial will provide enough data of the therapy’s benefits in ALS to allow a resubmission of a marketing application seeking regulatory approval.

BrainStorm, FDA map out next steps for Phase 3b testing of NurOwn

The U.S. Food and Drug Administration (FDA) has granted a Type A meeting to BrainStorm Cell Therapeutics to discuss the agency&#8217;s refusal to review <a href="https://alsnewstoday.com/nurown/">NurOwn</a> as a treatment for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
According to the FDA, <a href="https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/otat-type-meetings">type A meetings</a> are used for &#8220;an otherwise stalled product development program,&#8221; to talk about and settle differences between regulators and the developer of a potential therapy.
The upcoming meeting has been set for Jan. 11.
&#8220;We look forward to the Type A meeting which will provide an opportunity to discuss the path forward for NurOwn in ALS, including a possible Advisory Committee Meeting,&#8221; Chaim Lebovits, CEO of <a href="https://brainstorm-cell.com/">BrainStorm</a>, said in a <a href="https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-announces-type-a-meeting-with-fda-granted-for-nurown-301710196.html">company press release</a>.
The meeting will focus on the contents of a refusal to file letter issued by the FDA following BrainStorm&#8217;s new Biologics License Application (BLA) for the stem cell-based therapy.
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<h3>BrainStorm seeking new &#8216;path forward&#8217; for NurOwn</h3>
NurOwn is a cell-based therapy that requires first harvesting mesenchymal stem cells from a patient’s bone marrow. This is followed by a period of cell maturation, in which cells are induced to produce large amounts of signaling molecules that promote nerve cell health and growth. The modified cells are then returned to the patient via a spinal canal injection.
BrainStorm carried out a <a href="https://clinicaltrials.gov/ct2/show/NCT03280056">Phase 3 trial (NCT03280056)</a> to test the safety and efficacy of NurOwn in a group of 189 adults with rapidly progressing ALS. Patients received three injections of either NurOwn or a placebo, given every other month, and were then followed for about seven months (28 weeks).
Results showed that NurOwn was not significantly more effective than a placebo at slowing disease progression, as assessed with the ALS Functional Rating Scale-Revised (ALSFRS-R). This meant that the trial failed to meet its <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">primary goal</a>.
However, Brainstorm argued that the large proportion of patients with advanced disease in the trial may have masked NurOwn’s effects.
Such a population already has the lowest scores in some subscales of the ALSFRS-R, which creates a &#8220;floor effect&#8221; that prevents changes in disease progression from being properly detected, the company said.
Indeed, <a href="https://alsnewstoday.com/news/nurown-continues-show-benefit-rapidly-advancing-als/">subsequent analyses</a> that excluded patients with more severe ALS showed that the therapy has the potential to slow disease progression in a clinically meaningful manner compared with a placebo.
However, the <a href="https://alsnewstoday.com/news/fda-declines-considering-nurown-als/">FDA still declined to review</a> the BLA requesting NurOwn’s approval, citing insufficient evidence of effectiveness to support it. Regulators also cited concerns related to chemistry, manufacturing, and control procedures.
Faced with the FDA’s rejection, Brainstorm <a href="https://alsnewstoday.com/news/brainstorm-files-fda-meeting-new-bid-nurown-approval/">submitted a request</a> for the Type A meeting to discuss the situation.
Along with the request, the company provided an extensive briefing package addressing the FDA’s concerns, expressing confidence in “achieving quick alignment with the FDA” on these matters, Lebovits said in the <a href="https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-submits-type-a-meeting-request-to-us-food-and-drug-administration-301700042.html">press release</a> concerning the submission.
[quote align=&#8221;center&#8221;]We believe that an advisory committee meeting would serve as an important part of the review process[/quote]
The FDA’s refusal to review NurOwn also prompted a response from the ALS community. Two open letters in favor of NurOwn’s review were published, one from <a href="https://alsnewstoday.com/news/als-patients-given-nurown-call-fda-meeting-discuss-refusal/">a group of ALS patients</a> who received NurOwn during clinical testing, and another authored by U.S. military veterans with ALS.
The letters urged the FDA to hold a public advisory committee meeting to discuss the therapy with patients and ALS experts — including healthcare professionals who followed patients treated with NurOwn — and allow their voices to be heard and considered in the debate.
At the scheduled Type A meeting, Brainstorm will focus on securing an advisory committee meeting as the next step for a potential approval of NurOwn as an ALS therapy.
&#8220;We believe that an advisory committee meeting would serve as an important part of the review process and would provide an open forum for BrainStorm, together with medical experts, statisticians, patients and other members of the ALS community to discuss the body of clinical evidence supporting NurOwn,” Lebovits said.
The company plans to provide further updates after receiving the minutes from the meeting, or “when we have more clarity on the next steps in the approval process,” Lebovits added.

Tag: meeting

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