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Treatment with <a href="https://brainstorm-cell.com/science/#msc-cells">NurOwn</a> (debamestrocel), which BrainStorm Cell Therapeutics is developing for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), may bring about changes in biomarkers of inflammation and neurodegeneration that predict clinical outcomes.
The findings come from the <a href="https://clinicaltrials.gov/study/NCT03280056">Phase 3 trial (NCT03280056)</a> that tested NurOwn against a placebo in 189 adults with rapidly progressing ALS. The trial <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">failed to meet its main goal</a> of slowing disease progression, but showed <a href="https://alsnewstoday.com/news/nurown-benefits-patients-less-severe-als-analyses-show/">promise</a> in those with less advanced disease.
“These findings are encouraging and provide preliminary evidence that debamestrocel may be effective in treating ALS. The impact on biomarkers suggests debamestrocel targets inflammation and neurodegeneration,” Chaim Lebovits, president and CEO of <a href="https://brainstorm-cell.com">BrainStorm</a>, said in a <a href="https://ir.brainstorm-cell.com/2024-04-10-BrainStorm-Cell-Therapeutics-Announces-Peer-reviewed-Publication-of-Biomarker-Data-from-NurOwns-R-Phase-3-Clinical-Trial-in-ALS">company press release</a>.
The study, “<a href="https://onlinelibrary.wiley.com/doi/10.1002/mus.28093">Debamestrocel multimodal effects on biomarker pathways in amyotrophic lateral sclerosis are linked to clinical outcomes</a>,” was published in Muscle &amp; Nerve. It was funded by BrainStorm.
NurOwn is a cell-based therapy that involves harvesting mesenchymal stem cells from a patient’s bone marrow. These stem cells, which can develop into a variety of cell types, are then grown in a lab to secrete large amounts of neurotrophic factors, or molecules that boost nerve cell heath and survival.
After the modified stem cells are expanded into the millions, they are returned to the patient via an injection into the spinal canal, where they should produce high levels of neurotrophic factors and help slow disease progression.
The previous Phase 3 trial tested the therapy in adults with rapidly progressing ALS, most of whom had advanced disease. An analysis showed that levels of neurofilament light chain (NfL), a biomarker of nerve cell damage, in the spinal fluid were significantly lower after treatment with NurOwn and this reduction was <a href="https://alsnewstoday.com/news/nurown-trial-slower-als-progression-tied-lower-nfl-levels/">linked to slower disease progression</a>.
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<h3>NurOwn&#8217;s effect on disease biomarkers</h3>
To know more about the impact of NurOwn on disease biomarkers, researchers examined 45 biomarkers in spinal fluid samples from 185 of the participants.
Compared with a placebo, NurOwn resulted in significant changes in 16 biomarkers of neuroinflammation, eight biomarkers of neurodegeneration, and nine biomarkers of neuroprotection after 20 weeks.
Similar findings were obtained with the participants with less advanced ALS who saw the greatest clinical benefits with NurOwn, but also in those with more advanced disease, &#8220;suggesting debamestrocel remains biologically active regardless of clinical progression,&#8221; the researchers wrote. &#8220;The results &#8230; highlight a pattern across biomarkers relative to placebo, with debamestrocel reducing levels of neuroinflammation (reducing pro-inflammatory biomarkers, and elevating anti-inflammatory biomarkers), lowering markers of neurodegeneration, and elevating neuroprotective biomarkers.&#8221;
The researchers identified three biomarkers that seemed to predict clinical responses to NurOwn. For example, lower levels of NfL at the start of the study, that is, its baseline, predicted slower rates of disease progression. Also, the greater the reduction in NfL after NurOwn treatment, the smaller the disease severity progression.
The other two biomarkers were baseline levels of TGF-beta1, which indicated less neuroinflammation, and changes in galectin-1 that indicated greater neuroprotection, both of which also predicted slower disease progression.
“The identification of biomarkers across different pathways could be an indication of the mechanism of action of debamestrocel of balancing the immune response through modulation of inflammation while at the same time preserving the dynamics of the interplay with neurodegenerative processes,” the researchers wrote.
“The publication of these findings is important, because it demonstrates a potential biologic mechanism by which modified mesenchymal stem cells (debamestrocel) may benefit patients with ALS,” said Anthony J. Windebank, MD, a professor of neurology at Mayo Clinic College of Medicine and Science in Rochester, and one of the study authors.
While data from the Phase 3 trial were <a href="https://alsnewstoday.com/news/fda-advisory-committee-votes-not-enough-efficacy-nurown-als/">deemed insufficient</a> to support an approval by the U.S. Food and Drug Administration (FDA), leading BrainStorm to <a href="https://alsnewstoday.com/news/brainstorm-drops-application-nurown-als-regroup/">withdraw its application</a> in October, the company plans a Phase 3b trial to test NurOwn in people with less advanced disease.
The two-part trial will enroll about 200 participants whose symptoms started within the last two years. They will receive NurOwn or a placebo for six months along with standard ALS treatments. For the next six months, all will then receive the experimental medication.
The trial&#8217;s protocol and planned statistical analyses have been reviewed by the FDA under a special protocol assessment and deemed adequate to support a future regulatory application.
“Biomarkers are becoming an increasingly important part of drug development in ALS,” said Stacy Lindborg, PhD, co-CEO of BrainStorm. “We look forward to confirming these findings in our upcoming Phase 3b trial, which is in planning for the most expeditious path forward to bring NurOwn to people living with ALS.”

Certain spinal fluid biomarkers may predict responses to NurOwn

The U.S. Food and Drug Administration (FDA) has agreed on the design of a Phase 3b trial that will test the investigational cell-based therapy <a href="https://alsnewstoday.com/nurown/">NurOwn</a> (debamestrocel) in <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) patients with less advanced disease.
The developer, <a href="https://brainstorm-cell.com/">BrainS</a><a href="https://brainstorm-cell.com/">torm Cell Therapeutics</a>, plans to launch the trial this year, and should the data be positive, it will back an application seeking regulatory approval of the therapy.
The FDA reviewed the clinical trial protocol and statistical analyses under what’s known as a Special Protocol Assessment (SPA). Developers can request these evaluations to make sure the agency believes a trial’s design is generally adequate to support a future regulatory application. Still, the SPA agreement is not a guarantee of the FDA’s approval of all aspects of the trial or the therapy’s potential clearance.
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“We are pleased to have reached an agreement with the FDA on key elements of the Phase 3b trial design that provides a potential path forward towards obtaining regulatory approval,&#8221; Chaim Lebovits, president and CEO of BrainStorm, said in a <a href="https://ir.brainstorm-cell.com/2024-04-09-BrainStorm-Cell-Therapeutics-Announces-Agreement-with-FDA-on-a-Special-Protocol-Assessment-SPA-for-Phase-3b-Trial-in-ALS">company press release</a>.
“BrainStorm&#8217;s ultimate goal is to provide a new treatment option that can help patients afflicted with ALS, and we believe that the SPA potentially brings us one step closer to this goal,” Lebovits added.
<h3>BrainStorm&#8217;s new effort</h3>
The Phase 3b trial has <a href="https://alsnewstoday.com/news/brainstorm-making-cuts-support-new-trial-nurown-als/">been in the works since last year</a>, when U.S. regulators indicated that evidence from completed clinical trials was insufficient to back NurOwn’s approval.
“We have worked with leading neurologists, scientists, and members of the ALS community to create a robust study designed to evaluate the effectiveness and safety of NurOwn,” said Stacy Lindborg, PhD and co-CEO of BrainStorm. “Over the past year, we&#8217;ve assembled an excellent team in clinical development that is highly qualified to execute this trial with excellence.”
NurOwn involves collecting a patient’s own mesenchymal stem cells (MSCs) from the bone marrow and engineering them in a lab to secrete large amounts of signaling molecules that promote nerve cell health.
The modified cells are then expanded and returned to the patient via injections into the spinal canal, where they’re expected to help protect the motor nerve cells that are characteristically lost in ALS, thereby slowing disease progression.
An earlier <a href="https://clinicaltrials.gov/study/NCT03280056">Phase 3 trial (NCT03280056)</a> tested the therapy in adults with rapidly progressing ALS, most of whom had advanced disease. The trial <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">failed to show</a> a statistically significant slowing of disease progression with NurOwn when compared with a placebo.
Still, additional analyses indicated that <a href="https://alsnewstoday.com/news/nurown-benefits-patients-less-severe-als-analyses-show/">disease progression was slowed</a> among the subgroup of patients with less severe disease. BrainStorm applied for approval of NurOwn in 2022 on the basis of those promising data, but the FDA <a href="https://alsnewstoday.com/news/fda-declines-considering-nurown-als/">declined to consider the application</a>, citing that the data were insufficient.
The company later used a special process called “<a href="https://alsnewstoday.com/news/als-therapy-maker-brainstorm-secures-adcom-over-fda-objection/">file over protest</a>” to proceed with its application anyway, but the company later <a href="https://alsnewstoday.com/news/brainstorm-drops-application-nurown-als-regroup/">withdrew its application</a> after an FDA advisory committee <a href="https://alsnewstoday.com/news/fda-advisory-committee-votes-not-enough-efficacy-nurown-als/">echoed</a> the FDA’s earlier sentiment.
BrainStorm has been communicating with FDA regulators since then, planning for the launch of the Phase 3b trial, which it hopes will provide the agency with the evidence needed to approve NurOwn.
<h3>2-part study planned</h3>
The multicenter Phase 3b trial, called BCT-006-US, will be a <a href="https://alsnewstoday.com/news/mda-2024-phase-3b-trial-aims-support-nurown-efficacy-als/">two-part study</a> designed to evaluate NurOwn’s safety and efficacy in early ALS patients whose symptoms emerged within the last two years.
“This trial builds on valuable insights from our earlier studies and will enroll people living with ALS who are earlier in the course of their disease,” Lindborg noted.
Around 200 adult participants will be enrolled and randomly assigned to receive three injections of NurOwn or a placebo, given once every eight weeks for about six months. All participants will then receive another three injections of NurOwn in the study&#8217;s second part, which will also last six months.
Participants will also be allowed to continue treatment with approved standard-of-care <a href="https://alsnewstoday.com/als-treatment/">ALS therapies</a> throughout the study.
The trial’s main goal is to evaluate whether NurOwn slows disease progression compared with a placebo, as assessed by changes in the ALS Functional Rating Scale-Revised (ALSFRS-R) over the first 24 weeks.
Final conclusions on whether this goal was met will rely on a combined assessment of functional changes and survival, to take into account any deaths observed during the study.
Samples of blood and cerebrospinal fluid — the liquid that surrounds the brain and spinal cord — will be collected during the trial to evaluate biomarkers of neuroinflammation, neurodegeneration, and neuroprotection.
Safety will be monitored by an independent Data Monitoring Committee throughout the study, according to the company.
“Based on the evidence generated on NurOwn to date, we have a trial that we&#8217;re optimistic will be positive,” Lindborg said. “We&#8217;ve been parallel processing to enable us to deliver the first dose in the trial in 2024, and we&#8217;re anxious to get started.&#8221;

FDA OKs Phase 3b trial design for NurOwn in less advanced ALS

Note: This story was updated March 6, 2024, to correct the poster was presented by Brainstorm’s executive vice president and chief development officer Bob Dagher.
A pivotal, Phase 3b clinical trial is planned to test the cell-based therapy <a href="https://alsnewstoday.com/nurown/">NurOwn</a> (debamestrocel) in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), the treatment&#8217;s developer, <a href="https://brainstorm-cell.com" rel="nofollow">Brainstorm Cell Therapeutics</a>, announced.
The study&#8217;s design, based on positive findings from a previous Phase 3 trial in patients with less advanced disease, is under U.S. Food and Drug Administration (FDA) review.
In that earlier trial, NurOwn was seen to <a href="https://alsnewstoday.com/news/nurown-benefits-patients-less-severe-als-analyses-show/">significantly slow disease progression</a> in people with less severe ALS, but it failed at the study&#8217;s main goal of slowing progression across all treated patients. An FDA committee later decided that trial data were <a href="https://alsnewstoday.com/news/fda-advisory-committee-votes-not-enough-efficacy-nurown-als/">insufficient to support NurOwn&#8217;s effectiveness</a> in ALS.
&#8220;We are committed to doing everything we can to make NurOwn available to ALS patients in need,&#8221; Chaim Lebovits, Brainstorm&#8217;s president and CEO, said in a <a href="https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-to-unveil-phase-3b-nurown-trial-design-at-mda-clinical-and-scientific-conference-302072354.html">company press release</a>.
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<h3>NurOwn, a cell therapy, showed potential in people with less advanced ALS</h3>
The company anticipates that the Phase 3b trial will confirm NurOwn&#8217;s benefits in this patient group, potentially supporting a new application requesting the therapy&#8217;s approval for people with mild-to-moderate ALS.
&#8220;The Phase 3b trial takes into account learning from NurOwn’s clinical development program, in addition to the latest insight from the ALS community,&#8221; Stacy Lindborg, co-CEO of Brainstorm, said in a statement to ALS News Today.
&#8220;We’ve simulated the operating characteristics of the trial and are confident this trial is a robust design which will rigorously assess the efficacy and safety of NurOwn,&#8221; she added.
Brainstorm reported <a href="https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-submits-special-protocol-assessment-spa-request-to-fda-for-phase-3b-trial-of-nurown-in-als-302069799.html" rel="nofollow">submitting a special protocol assessment (SPA)</a> for the trial to the FDA in late February. An SPA is used to request FDA review of a trial&#8217;s planned design to help ensure that positive results could feasibly support an application for therapy approval.
&#8220;We are grateful for the FDA&#8217;s ongoing engagement and look forward to its feedback and to finalizing the SPA,&#8221; Bob Dagher, MD, Brainstorm&#8217;s executive vice president and chief development officer, said in the release.
Details of the Phase 3b trial will be finalized following the FDA&#8217;s review and response. In the meantime, Dagher presented the planned study design at the Muscular Dystrophy Association&#8217;s 2024 Clinical and Scientific Conference, detailed in the poster &#8220;<a href="https://www.mdaconference.org/abstract-library/design-of-a-phase-3b-trial-of-debamestrocel-in-als/">Design of A Phase 3B Trial of Debamestrocel in ALS</a>.&#8221;
<h3>Planned yearlong trial to enroll 200 people with mild-to-moderate ALS</h3>
This yearlong, two-part study is expected to recruit about 200 adults, ages 18 to 75, with mild-to-moderate disease and <a href="https://alsnewstoday.com/symptoms-of-als/">ALS symptom</a> onset less than two years before enrolling. Eligible participants also need to meet certain criteria surrounding physical function and breathing ability, and patients using approved <a href="https://alsnewstoday.com/als-treatment/">ALS treatments</a> must be on a stable dose before a screening for the trial.
In its planned first part, patients will be randomly assigned to NurOwn treatment or a placebo for about six months (24 weeks) while remaining on standard care. In a second part, all enrolled will be treated with NurOwn for another six months. Both placebo and NurOwn will be given by injection into the spine canal (intrathecal injection) every eight weeks.
The planned study&#8217;s main goal will be determining if NurOwn slows patients&#8217; loss of functional abilities, as measured by changes from the trial&#8217;s start in Revised ALS Functional Rating Scale (ALSFRS-R) scores. It also plans to assess changes in measures of muscle strength and breathing ability, as well as survival outcomes.
Patients will be asked to complete a questionnaire on their health status and life quality, and interviews will be conducted with caregivers of participants.
&#8220;The planned study will enroll patients earlier in their disease course, as we believe that this is the appropriate patient population in which the course of the disease can be accurately measured using ALSFRS-R,&#8221; Dagher said.
NurOwn treatment involves collecting mesenchymal stem cells from a patient&#8217;s bone marrow and engineering them in a lab to secrete high levels of neurotrophic factors, signaling molecules that promote nerve health. The modified stem cells then are injected into the patient&#8217;s spinal canal, with the goal of slowing the progressive nerve damage that <a href="https://alsnewstoday.com/causes-of-als/">causes ALS</a>.
The earlier <a href="https://clinicaltrials.gov/study/NCT03280056">Phase 3 trial (NCT03280056)</a>, which ended in 2020, tested NurOwn against a placebo in 189 adults with rapidly progressing ALS, most of whom had advanced disease. Although <a href="https://alsnewstoday.com/news/nurown-continues-show-benefit-rapidly-advancing-als/">some promising trends</a> were seen in patients with less severe disease, the study overall <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">failed to show</a> a statistically significant difference in disease progression rates between patients on NurOwn and those given a placebo.
<h3>FDA, advisory group found efficacy data lacking in previous approval requests</h3>
Brainstorm <a href="https://alsnewstoday.com/news/brainstorm-plans-filing-nurown-approval-us-corrected-data/">applied to the FDA for NurOwn&#8217;s approval</a> in 2022, hoping that analyses showing beneficial Phase 3 trends would be enough to support treatment efficacy. The FDA initially <a href="https://alsnewstoday.com/news/fda-declines-considering-nurown-als/">refused to consider the application</a>, citing insufficient data.
Brainstorm then used a procedure called <a href="https://alsnewstoday.com/news/als-therapy-maker-brainstorm-secures-adcom-over-fda-objection/">file over protest</a> to seek a review from an FDA advisory committee. But that committee also decided that available data were not enough to support therapy effectiveness, and Brainstorm <a href="https://alsnewstoday.com/news/brainstorm-drops-application-nurown-als-regroup/">withdrew its application</a> in October.
Since then, the company has been <a href="https://alsnewstoday.com/news/brainstorm-fda-map-out-next-steps-nurown-phase-3b-testing/">working with the FDA</a> on the design of a confirmatory Phase 3b trial — planned to enroll patients at sites across the U.S. — that it hopes will provide the evidence needed for NurOwn&#8217;s approval.
&#8220;We have given careful consideration to a Phase 3b trial that will conclusively demonstrate the efficacy and safety of NurOwn and support a new [application seeking FDA approval],&#8221; Dagher said.
&#8220;Our previous studies have provided us with valuable insight into the NurOwn treatment effect,&#8221; he added. &#8220;We believe that by incorporating these learnings into the design of a confirmatory study we can maximize the prospects of a successful outcome.&#8221;

MDA 2024: Planned Phase 3b trial aims to support NurOwn’s approval

<a href="https://brainstorm-cell.com/" rel="nofollow">BrainStorm Cell Therapeutics</a> has received patents in Europe, Australia, and Israel covering the use of investigational <a href="https://alsnewstoday.com/nurown/">NurOwn</a> and NurOwn exosomes in treating <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) and other neurological disorders.
The European patent specifically covers the use of an isolated population of mesenchymal stem cells — the cells used to produce NurOwn — in people with ALS. It also covers a method of qualifying whether a cell population is suitable for treating ALS.
&#8220;The recent acquisition of the European patent for our unique [NurOwn] cell population marks an important step in safeguarding our proprietary NurOwn technology, particularly for ALS treatment,” Chaim Lebovits, BrainStorm&#8217;s CEO, said in a <a href="https://www.prnewswire.com/news-releases/brainstorm-granted-patents-for-allogeneic-exosome-platform-product-in-neurological-disorder-treatments-302022322.html">company press release</a>.
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<h3>NurOwn aims to treat ALS by promoting nerve cell growth and survival</h3>
&#8220;Securing this European patent, alongside our existing patents in the US, Canada, Israel, Brazil, and Japan, enhances our capability to forge new global commercial partnerships, further expanding the reach of NurOwn,&#8221; he added.
The Australian and Israeli patents cover the use of exosomes — small vesicles released by virtually all cells that contain proteins and other molecules important for cellular communication — derived from NurOwn cells in treating neurodegenerative conditions.
NurOwn is an experimental cell-based therapy designed to slow ALS progression and extend survival by boosting nerve cell survival.
It involves collecting mesenchymal stem cells — which can differentiate into a variety of cell types — from a patient’s bone marrow and maturing them in the lab into cells that produce high levels of neurotrophic factors, or signaling molecules that promote nerve cell growth and survival.
The mature cells, called MSC-NFTs, then are returned to the patient via injections into the spinal canal, where they release the molecules protective of motor neurons, which is expected to slow disease progression.
&#8220;The Australian patent, which is our inaugural grant for the specialized MSC-NTF cell exosomes, represents a pivotal achievement in the evolution of our exosome technology,&#8221; Lebovits said.
The company also is developing a distinct therapy using exosomes derived from MSC-NFT cells, expected to transport neurotrophic factors and other signaling molecules to a patient&#8217;s nerve cells.
BrainStorm completed a <a href="https://clinicaltrials.gov/study/NCT03280056">Phase 3 trial (NCT03280056)</a> of NurOwn&#8217;s safety and efficacy in 189 adults with rapidly progressing ALS. Participants received three injections, given at two-month intervals, of either NurOwn or a placebo.
Treatment <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">failed to significantly slow disease progression</a>, based on the ALS Functional Rating Scale-Revised (ALSFRS-R), trial results showed. But BrainStorm argued that the lack of a significant effect could be due to a floor effect, meaning treated patients had such advanced disease that a slowing in disease progression could not be detected.
A <a href="https://alsnewstoday.com/news/nurown-benefits-patients-less-severe-als-analyses-show/">clinically meaningful response</a> to NurOwn treatment was seen among a patient group with less severe disease.
<h3>New Phase 3 clinical trial of NurOwn in ALS patients possible</h3>
A U.S. Food and Drug Administration (FDA) advisory committee subsequently found that <a href="https://alsnewstoday.com/news/fda-advisory-committee-votes-not-enough-efficacy-nurown-als/">evidence was lacking to support NurOwn</a> in treating ALS, leading BrainStorm to <a href="https://alsnewstoday.com/news/brainstorm-drops-application-nurown-als-regroup/">withdraw its application for NurOwn&#8217;s approval</a>.
Company and FDA officials recently discussed plans for a <a href="https://alsnewstoday.com/news/brainstorm-fda-map-out-next-steps-nurown-phase-3b-testing/">confirmatory Phase 3b trial</a> of the cell therapy, intended to ensure the study&#8217;s design meets agency requirements to support a future application.
NurOwn technology has been designated an orphan drug by the FDA and the European Medicines Agency as a potential treatment of ALS. This status is given to therapies aiming to treat rare diseases, and it provides developers with benefits that include exemption from regulatory fees, assistance with clinical trial protocols, and several years of market exclusivity if the therapy is approved.

NurOwn and its exosomes given patents in Europe, Australia, Israel

<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

<a href="https://brainstorm-cell.com/" rel="nofollow">BrainStorm Cell Therapeutics</a> is making strategic adjustments — including cuts in its workforce — to accelerate the clinical development of <a href="https://alsnewstoday.com/nurown/">NurOwn</a> as an <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) treatment.
The decision follows the recent <a href="https://alsnewstoday.com/news/brainstorm-drops-application-nurown-als-regroup/">withdrawal of its regulatory application</a> with the U.S. Food and Drug Administration (FDA) seeking the therapy&#8217;s approval, after an FDA advisory committee overwhelmingly decided that available data from a <a href="https://clinicaltrials.gov/study/NCT03280056">Phase 3 clinical trial (NCT03280056)</a> were <a href="https://alsnewstoday.com/news/fda-advisory-committee-votes-not-enough-efficacy-nurown-als/">insufficient to support NurOwn&#8217;s efficacy</a> 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.
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<h3>&#8216;Steadfast in our goal to make NurOwn available to the ALS community&#8217;</h3>
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 <a href="https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-announces-strategic-realignment-prioritizing-nurown-for-the-treatment-of-als-301965642.html">company press release</a>.
NurOwn&#8217;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&#8217;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&#8217;s design and for the upcoming FDA meeting.
A cell-based therapy, NurOwn involves collecting a person&#8217;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, <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">failed to meet its main goal</a> 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.
Based on available trial data, the FDA <a href="https://alsnewstoday.com/news/nurown-trial-data-lacking-brainstorm-fda-approval-review/">discouraged a regulatory filing</a>, and later <a href="https://alsnewstoday.com/news/fda-declines-considering-nurown-als/">refused to review the filed application</a>, citing insufficient evidence of the therapy’s benefits.
But Brainstorm <a href="https://alsnewstoday.com/news/als-therapy-maker-brainstorm-secures-adcom-over-fda-objection/">used a ‘filed over protest’ procedure</a> to move its application ahead, allowing for the Sept. 27 advisory committee meeting that, in a 17-1 vote, found insufficient support.
<h3>Possibility of a floor effect masking benefits in earlier Phase 3 trial</h3>
The company has argued that further analyses of NurOwn data indicate the presence of a <a href="https://alsnewstoday.com/news/mda-2023-issues-als-scale-noted-nurown-trial-failure-analysis/">floor effect</a><a href="https://alsnewstoday.com/news/mda-2023-issues-als-scale-noted-nurown-trial-failure-analysis/"> in the ALSFRS-R</a>, 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&#8217;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&#8217;s use and a placebo were missed. This hypothesis is supported by the therapy being shown <a href="https://alsnewstoday.com/news/nurown-benefits-patients-less-severe-als-analyses-show/">to slow disease progression</a> in trial patients with less severe disease, where the impact of the floor effect isn&#8217;t expected to be as profound.
“While the Phase 3 trial was confounded by the ALSFRS-R scale&#8217;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 <a href="https://alsnewstoday.com/news/fda-questions-nurown-efficacy-quality-ahead-advisory-panel/">questioning the presence</a> 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.

BrainStorm making cuts to support new trial, advance NurOwn for ALS

<a href="https://brainstorm-cell.com/">BrainStorm Cell Therapeutics</a> is withdrawing the application requesting U.S. approval of its cell-based therapy <a href="https://alsnewstoday.com/nurown/">NurOwn</a> for the treatment of <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The decision comes on the heels of a recent U.S. Food and Drug Administration (FDA) advisory committee meeting, in which experts ruled nearly unanimously that available data for the experimental therapy <a href="https://alsnewstoday.com/news/fda-advisory-committee-votes-not-enough-efficacy-nurown-als/">does not provide enough evidence</a> to support its effectiveness in ALS.
While an official decision from the FDA was expected in December, the withdrawal of the biological license application (BLA) means the agency no will longer review the data. BrainStorm has coordinated its decision to withdraw the BLA with the FDA, which regards the move as a withdrawal without prejudice for a future refiling.
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Meanwhile, the regulatory agency invited the company to request an expedited face-to-face meeting to discuss the next steps for NurOwn&#8217;s development. The company intends to use the meeting to explore a number of approaches, including the publication of emerging clinical data and an additional Phase 3b clinical study.
&#8220;After exploring possible options, we have reached this conclusion that the only path forward of NurOwn for ALS is to conduct another trial. Therefore, we&#8217;re withdrawing our BLA,&#8221; Chaim Lebovits, president and CEO of BrainStorm, said in a <a href="https://www.webcaster4.com/Player/Index?webcastId=49296&amp;g=824e82b3-5502-4572-b94f-9050e434ebcc&amp;uid=6296598&amp;sid=">company webcast</a> announcing the decision.
&#8220;We&#8217;re accepting [the] FDA&#8217;s invitation to have a face-to-face discussion on a Phase 3b trial, with the aim to reach an agreed-upon trial design,&#8221; he added. &#8220;We recognize the need to align with the FDA and will do all we can to deliver a valuable treatment option to the ALS community.&#8221;
Based on data from the earlier <a href="https://clinicaltrials.gov/study/NCT03280056">Phase 3 clinical trial (NCT03280056)</a>, the upcoming study &#8220;likely&#8221; will focus on a mild or less advanced patient population, said Stacy Lindborg, PhD, co-CEO of BrainStorm.
<h3>How NurOwn works</h3>
NurOwn is a cell-based therapy that involves collecting a patient’s stem cells from the bone marrow, engineering them in a laboratory so they produce high levels of signaling molecules that promote nerve health and growth, and then returning the modified cells directly to the patient through an injection into the spine.
A completed Phase 3 trial was designed to study the therapy against a placebo in a group of 189 people with rapidly-progressing ALS.
The trial <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">failed to meet its primary goal</a> of showing that NurOwn could slow disease progression on the ALS Functional Rating Scale-Revised (ALSFRS-R) scale. But additional analyses showed it could slow the decline in that scale in a group of patients with less-advanced disease.
This prompted BrainStorm to submit the data to the FDA back in 2021, at which point the agency, citing lack of clinical evidence, <a href="https://alsnewstoday.com/news/nurown-trial-data-lacking-brainstorm-fda-approval-review/">discouraged the filing</a> of a regulatory application.
Later findings from the company showed that the lack of a significant effect could be attributable to a so-called <a href="https://alsnewstoday.com/news/mda-2023-issues-als-scale-noted-nurown-trial-failure-analysis/">floor effect</a>, where patients in the trial had such advanced disease that scores could not decrease even further as the disease progressed. That meant a slowdown in disease decline would not be detected.
In line with this, an analysis focusing only on patients with less-severe disease, which were not expected to be affected by this floor effect, suggested that NurOwn <a href="https://alsnewstoday.com/news/nurown-benefits-patients-less-severe-als-analyses-show/">could slow disease progression</a>, compared with a placebo.
This time, <a href="https://alsnewstoday.com/news/brainstorm-plans-filing-nurown-approval-us-corrected-data/">the company submitted an application</a> in August 2022, which the FDA <a href="https://alsnewstoday.com/news/fda-declines-considering-nurown-als/">refused to consider</a> in November of that year. Still, BrainStorm decided to &#8220;<a href="https://alsnewstoday.com/news/als-therapy-maker-brainstorm-secures-adcom-over-fda-objection/">file over protest</a>,&#8221; which granted it an advisory committee meeting where experts reviewed not only the clinical data, but also reports of patient and clinician experiences with NurOwn.
The committee, however, <a href="https://alsnewstoday.com/news/fda-questions-nurown-efficacy-quality-ahead-advisory-panel/">failed to detect evidence of a floor effect</a> in the trial, and cautioned that the analyses conducted after the trial ended are highly prone to false-positive results. That led to a 17-to-1 vote that the available clinical evidence was not enough to support the benefits of NurOwn in ALS patients.
&#8220;We are confident in the data supporting the value of NurOwn as an addition to the options for treating ALS, and we have every desire to bring it to the ALS community,&#8221; Lebovits said in a company <a href="https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-to-meet-with-us-fda-to-discuss-development-plan-for-nurown-as-a-treatment-of-als-301960219.html">press release</a>.
<h3>Pivotal trial in the offing</h3>
&#8220;We look forward to working with the FDA to define the path forward. We understand that an additional pivotal trial will be necessary, and we are doing everything in our power to execute on this as quickly as possible,&#8221; he added.
The withdrawal also enables BrainStorm to finally tell patients who participated in the trial whether they were initially given a placebo or the cell therapy, the company said on the webcast.
&#8220;Information regarding randomization will be provided to the principal investigators at each of the clinical sites, who will provide information directly to participants and their families,&#8221; said Lindborg.

BrainStorm drops FDA application for NurOwn

In a nearly unanimous vote, an advisory committee to the U.S. Food and Drug Administration (FDA) said there&#8217;s not enough evidence to support the efficacy of the experimental stem cell therapy <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).
The committee voted on a single question in its meeting: &#8220;Do the data presented demonstrate substantial evidence of effectiveness for treatment of mild to moderate ALS?&#8221;
In all, 17 of the 19 committee members voted no. There was one yes vote and one abstention.
An <a href="https://alsnewstoday.com/news/fda-final-approval-decision-brainstorms-nurown-als-due-december/">official decision from the FDA</a> on NurOwn is set to be handed down in December. The regulatory agency is not obligated to abide by the committee&#8217;s vote, but it usually does.
&#8220;The discussion in today&#8217;s advisory committee meeting, and the heartrending testimony of those living with ALS and their loved ones, underscores not only the need for regulatory flexibility but also for continuing research in the field,&#8221; Chaim Lebovits, president and CEO of <a href="https://brainstorm-cell.com/" rel="nofollow">BrainStorm Cell Therapeutics</a>, NurOwn&#8217;s developer, said in a <a href="https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-provides-update-on-fda-advisory-committee-meeting-to-review-nurown-for-the-treatment-of-als-301941169.html">company press release</a>, adding, &#8220;The people of BrainStorm will do everything in our power to fulfill the obligation we deeply feel we owe to the ALS community, and in the coming weeks we will explore all options available to us.&#8221;
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<h3>FDA found no evidence of so-called floor effect in trial</h3>
NurOwn is a cell-based therapy that involves harvesting stem cells from a patient&#8217;s bone marrow, engineering them in a laboratory so they secrete molecules that promote nerve health, and then infusing the cells back into the patient&#8217;s spine.
Following a decade of testing, BrainStorm submitted an application to the FDA last year seeking approval of NurOwn in the U.S. The agency initially <a href="https://alsnewstoday.com/news/fda-declines-considering-nurown-als/">refused to review</a> the application, saying there was not enough evidence to support an approval.
However, but BrainStorm forced a new review and an advisory committee meeting using the <a href="https://alsnewstoday.com/news/als-therapy-maker-brainstorm-secures-adcom-over-fda-objection/">FDA’s “file over protest” procedure</a>.
BrainStorm&#8217;s application includes data from several clinical trials, including a large <a href="https://clinicaltrials.gov/ct2/show/NCT03280056">Phase 3 study (NCT03280056)</a> that tested NurOwn against a placebo in 189 people with rapidly-progressing ALS.
The study aimed to show that NurOwn could slow the progression of the disease, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), a standardized measure that assesses a person&#8217;s ability to perform activities of daily living. But final results showed <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">no difference in progression</a> between patients given NurOwn or a placebo.
The company argued that this might be due to a so-called <a href="https://alsnewstoday.com/news/mda-2023-issues-als-scale-noted-nurown-trial-failure-analysis/">floor effect</a> —  where some patients had ALSFRS-R scores so low that they couldn&#8217;t meaningfully get lower.
In post hoc analyses done once the study was over, the company analyzed only subsets of patients expected not to have a floor effect. Those results <a href="https://alsnewstoday.com/news/nurown-benefits-patients-less-severe-als-analyses-show/">generally suggested</a> slower disease progression with NurOwn compared with a placebo.
In briefing documents put out before the committee meeting, the FDA said it <a href="https://alsnewstoday.com/news/fda-questions-nurown-efficacy-quality-ahead-advisory-panel/">did not find evidence</a> of a floor effect in the patients that BrainStorm had flagged. The agency also cautioned that post hoc analyses are heavily prone to false-positive results, and, overall, reiterated its stance that there are not enough data to support an approval of NurOwn.
[quote=&#8221;center&#8221;]The committee&#8217;s vote was a sad outcome for the ALS community, who have too few options to help manage this merciless and deadly disease.[/quote]
The advisory committee has now strongly voted that the available data are not enough to demonstrate that NurOwn is effective in ALS — a decision that further supports a potential rejection by the FDA.
&#8220;The committee&#8217;s vote was a sad outcome for the ALS community, who have too few options to help manage this merciless and deadly disease,&#8221; said Stacy Lindborg, PhD, co-CEO of BrainStorm.
&#8220;We firmly believe that the totality of data presented for NurOwn today provide a compelling case for approval, with clinical evidence in those with less advanced disease supported by strong and consistent biomarker data that are predictive of clinical response,&#8221; Lindborg said.
Lindborg suggested that too little time was given during the meeting for BrainStorm to answer all of the committee&#8217;s questions.
&#8220;We truly did our best to make the NurOwn data clear to the FDA advisory committee. Unfortunately, had more time and opportunity been allowed, many remaining questions posed by advisory committee members could have been sufficiently addressed,&#8221; Lindborg said.

FDA advisory committee votes against NurOwn approval for ALS

The U.S. Food and Drug Administration (FDA) has shared its major concerns with data available for <a href="https://alsnewstoday.com/nurown/">NurOwn</a>, <a href="https://brainstorm-cell.com/" rel="nofollow">BrainStorm Cell Therapeutics</a>‘ experimental stem cell therapy for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
According to a new <a href="https://www.fda.gov/media/172403/download">briefing document</a> put out by the FDA, the agency believes that currently available clinical data do not provide substantial evidence to support NurOwn&#8217;s effectiveness in people with ALS. It also raised concerns about whether BrainStorm can reliably manufacture the therapy.
The document was released in advance of an FDA advisory committee meeting on NurOwn&#8217;s efficacy, set to take place today, Sept. 27.
[recommended-reading id=86692]
<h3>BrainStorm: &#8216;Floor effect&#8217; reason for NurOwn failure in Phase 3 ALS trial</h3>
NurOwn treatment involves harvesting mesenchymal stem cells (MSCs) from a patient’s bone marrow. The stem cells are engineered in a laboratory so that they secrete high levels of signaling molecules that promote nerve cell growth. Then, the cells are returned to the patient through injections into the spinal canal.
Late last year, the FDA <a href="https://alsnewstoday.com/news/fda-declines-considering-nurown-als/">refused to consider BrainStorm&#8217;s application</a> seeking approval of NurOwn as a <a href="https://alsnewstoday.com/approved-treatments-for-als/">treatment for ALS.</a>
The company then used the <a href="https://alsnewstoday.com/news/als-therapy-maker-brainstorm-secures-adcom-over-fda-objection/">FDA&#8217;s &#8220;file over protest&#8221; procedure</a> to ask the agency to review the application anyway, and a final agency decision on <a href="https://alsnewstoday.com/news/fda-final-approval-decision-brainstorms-nurown-als-due-december/">NurOwn is expected in December</a>.
At the advisory committee meeting, a panel of experts will review available data on NurOwn and offer a recommendation to the FDA. The panel has two questions to address: Do data submitted in support of NurOwn amount to &#8220;substantial evidence of effectiveness meeting the approval standard&#8221;? If not, discuss &#8220;potential designs&#8221; needed in a future trial to produce such evidence.
The FDA isn&#8217;t bound to abide by advisory committee opinions, but it usually follows them.
In its briefing document, the FDA reiterated a major concern it had voiced when it originally refused to consider BrainStorm&#8217;s application for NurOwn: Currently available clinical trial data don&#8217;t show the therapy works to slow ALS progression as intended.
BrainStorm sponsored a <a href="https://clinicaltrials.gov/ct2/show/NCT03280056">Phase 3 clinical trial (NCT03280056)</a> that compared NurOwn against a placebo in 189 people with rapidly progressing ALS.
The trial hoped to show that NurOwn slowed disease progression, as measured by changes over time in a measure of disease severity called the ALS Functional Rating Scale-Revised (ALSFRS-R).
However, the <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">study failed to show a significant difference</a> between patients given NurOwn or a placebo. Other measures of disease progression also generally did not show differences between the two groups.
BrainStorm has argued that the trial&#8217;s negative results might be explained by a <a href="https://alsnewstoday.com/news/mda-2023-issues-als-scale-noted-nurown-trial-failure-analysis/">&#8220;floor effect&#8221;</a> associated with the ALSFRS-R scale. Some patients with more advanced disease, it argued, may have had ALSFRS-R scores so low that they couldn&#8217;t meaningfully get lower, so statistical analyses were unable to accurately capture disease progression in these patients.
The company conducted post hoc analyses — statistical tests designed and run after the trial ends and all data have been collected — where researchers either excluded patients with the potential for a floor effect or included only those with less advanced disease. These analyses were generally positive, suggesting that <a href="https://alsnewstoday.com/news/nurown-benefits-patients-less-severe-als-analyses-show/">NurOwn slowed disease progression</a> compared with a placebo.
<h3>FDA questions &#8216;floor effect&#8217; and other findings meant to show NurOwn efficacy</h3>
According to the FDA, however, these analyses aren&#8217;t enough to show the therapy is effective. For one thing, the agency notes that post hoc analyses like these &#8220;in general have high risk of finding false positive results,&#8221; because the tests are being done on data that are already available.
&#8220;Such exploratory analyses provide little confidence on which to base regulatory decisions, and though they may serve to generate hypotheses for testing in future trials, cannot compensate for negative results in a well-controlled study,&#8221; the FDA wrote.
Moreover, the agency says that in its analysis of the data, it did not find evidence of a &#8220;floor effect.&#8221; If such an effect were present, it would be expected that ALSFRS-R scores would plateau when they couldn&#8217;t get lower.
In the FDA&#8217;s analysis, these scores tended to continuously change over the course of the trial, even for patients who BrainStorm flagged as having a &#8220;floor effect.&#8221; In fact, data suggest that ALSFRS-R scores tended to worsen slightly more quickly for patients given NurOwn than a placebo, and the overall change in scores was comparable between the two groups.
Collectively, these data show &#8220;the lack of efficacy of [NurOwn] over placebo cannot be explained by a floor effect,&#8221; the FDA document states.
The agency also noted that, over the course of the six-month trial, 10 patients given NurOwn died, as compared with three given a placebo. While the trial was not designed to assess survival, the agency said this finding &#8220;suggests the lack of efficacy of [NurOwn] on survival of patients with ALS.&#8221;
<h3>FDA concerns about manufacturing consistency and quality for NurOwn</h3>
In addition to concerns about NurOwn&#8217;s efficacy, the FDA also raised concerns about BrainStorm&#8217;s ability to consistently manufacture the therapy. According to the FDA, BrainStorm has failed to demonstrate that it can consistently produce the modified stem cells used for NurOwn, noting that the number of cells produced, as well as the amount of signaling molecules the cells make, has varied across lots for reasons that aren&#8217;t clear.
&#8220;FDA has concerns about the consistency of the manufacturing process and potential sources of product variability,&#8221; the agency wrote.
The briefing document notes that an evaluation of BrainStorm&#8217;s manufacturing and quality control data still is ongoing, and the upcoming advisory committee meeting will focus mainly on questions about the therapy&#8217;s demonstrated efficacy in clinical trials.
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&#8220;FDA recognizes the urgent unmet need for additional effective treatments for ALS. At the same time, the critical statutory requirements for approval of drugs and biologics include substantial evidence of effectiveness and evidence of safety, and demonstration of adequate product quality,&#8221; it writes.
&#8220;At this advisory committee meeting FDA is seeking to obtain input from the committee as to whether the available data can be considered to constitute substantial evidence of effectiveness to support regulatory approval of [NurOwn] for treatment of ALS.&#8221;
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Tag: NurOwn