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A European Medicines Agency (EMA) committee again has delayed issuing an opinion on whether to grant conditional approval to <a href="https://alsnewstoday.com/masitinib/">masitinib</a>, a potential add-on oral therapy for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
<a href="https://www.ab-science.com/">AB Science</a>, the therapy&#8217;s developer, now expects a recommendation in the second quarter of this year.
The postponement by the Committee for Medicinal Products for Human Use (CHMP) is due to outstanding issues regarding AB Science&#8217;s application requesting masitinib&#8217;s approval.
Responses to CHMP questions at this stage of the review process typically are given as oral explanations, and a meeting was scheduled for Jan. 24. But shortly before that date, the agency asked for written responses, an unusual request, AB Science stated in a <a href="https://www.globenewswire.com/news-release/2024/01/26/2818214/0/en/AB-Science-announces-an-update-in-the-marketing-authorization-application-of-masitinib-in-amyotrophic-lateral-sclerosis-at-the-European-Medicines-Agency.html">company press release</a>.
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<h3>New EMA guidelines were the cause of initial delayed opinion for masitinib</h3>
Written responses, AB Science noted in agreeing to the request, will provide CHMP with more detailed answers than likely would be possible in an oral presentation, and gives CHMP more time to evaluate the responses. A new oral meeting could be scheduled if major objections remain.
In September 2023, the company requested <a href="https://alsnewstoday.com/news/early-2024-likely-masitinib-eu-conditional-approval-decision-als/">more time to review masitinib production processes</a> to ensure they met recently implemented EMA guidelines regarding product manufacturing. CHMP accepted that request, which was expected to push into March a committee opinion on the therapy&#8217;s application, filed in 2022. The guidelines asked that companies review their manufacturing processes to identify and reduce an impurity called nitrosamine, which can increase cancer risk.
Masitinib is designed to block certain enzymes thought to drive inflammation and neurodegeneration in ALS, aiming to slow disease progression and ease <a href="https://alsnewstoday.com/symptoms-of-als/">disease symptoms</a>.
AB Science&#8217;s application is supported by the results of the <a href="https://clinicaltrials.gov/ct2/show/NCT02588677">Phase 2/3 </a><a href="https://clinicaltrials.gov/ct2/show/NCT02588677">AB10015</a><a href="https://clinicaltrials.gov/ct2/show/NCT02588677"> clinical trial (NCT02588677)</a>, which tested masitinib as an add-on to the approved ALS therapy <a class="c-link" href="https://alsnewstoday.com/rilutek-riluzole-for-als/" target="_blank" rel="noopener noreferrer" data-stringify-link="https://alsnewstoday.com/rilutek-riluzole-for-als/" data-sk="tooltip_parent">Rilutek</a> (riluzole) in 394 patients.
Findings showed that a 4.5 mg/kg daily dose of masitinib plus riluzole <a href="https://alsnewstoday.com/news-posts/2019/07/10/add-on-masitinib-slows-progression-of-als-final-phase-2-3-trial-results-show/">significantly slowed disease progression by 27%</a> versus riluzole and a placebo after nearly one year of treatment. These outcomes were in patients with so-called normal disease progression, defined as a monthly drop in the ALS Functional Rating Scale-Revised scores of less than 1.1 points.
Slower declines in quality of life and lung function also were observed with the combination therapy, particularly in patients progressing normally. In contrast, no changes were found among those progressing faster than usual.
Across the entire study population, no survival benefits with masitinib over a placebo were seen. Still, a recent analysis of trial data showed that patients with <a href="https://alsnewstoday.com/news/als-therapy-masitinib-works-best-add-on-moderate-disease-analysis/">mild or moderate ALS benefited most from adding masitinib</a>. These patients lived more than two years longer than those on riluzole alone, representing a 44% reduction in mortality risk.
<h3>Phase 3 trial evaluating masitinib as riluzole add-on in nearly 500 patients</h3>
Conditional approval in Europe is granted to medicines whose preliminary benefits outweigh their potential risks and fill an unmet medical need. But confirmatory clinical trials generally are required to support a full approval.
AB Science is sponsoring a global <a href="https://clinicaltrials.gov/ct2/show/NCT03127267">Phase 3 clinical trial (NCT03127267)</a> to confirm the benefits of adding masitinib to riluzole in about 495 patients. Eligible participants are randomly assigned to daily masitinib (4.5 or 6 mg/kg) plus riluzole or a placebo for 48 weeks (nearly one year). Assessed outcomes include changes in disease progression, lung function, muscle strength, quality of life, and survival.
If approved in Europe, masitinib is to be marketed under the brand name Alsitek.

CHMP delays opinion on masitinib, up for conditional EU approval

<a href="https://quralis.com/" rel="nofollow">QurAlis</a> soon expects to open its ongoing Phase 1 clinical trial testing QRL-201 in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) at sites in various European Union countries, including Germany, Belgium, the Netherlands, and Ireland.
The company&#8217;s announcement comes after these countries reviewed and accepted an application for the study. The <a href="https://www.clinicaltrials.gov/ct2/show/NCT05633459">Phase 1 ANQUR trial (NCT05633459)</a>, which is currently recruiting in Canada, could start enrolling patients at European sites by year&#8217;s end.
&#8220;This EU Clinical Trial Authorisation marks the second regulatory clearance for QRL-201 as we execute our global strategy focused on bringing breakthrough precision medicines to patients with ALS and other neurodegenerative diseases,&#8221; Kasper Roet, PhD, CEO and co-founder of QurAlis, said in a <a href="https://www.prnewswire.com/news-releases/quralis-receives-clinical-trial-authorisation-cta-in-european-union-eu-for-qrl-201-a-first-in-class-stathmin-2-precision-therapy-for-als-301839151.html">company press release</a>.
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<h3>Trial into safety of varying doses of experimental ALS treatment</h3>
ALS is a progressive neurodegenerative disorder that damages motor neurons, the nerve cells that control voluntary movements, leading to muscle weakness and muscle atrophy (shrinkage).
In most ALS cases, toxic aggregates of the TDP-43 protein accumulate in nerve cells, and they are believed to directly contribute to neurodegeneration. This protein normally works to process messenger RNA, an intermediated molecule made when genes are &#8220;read&#8221; to produce proteins.
<a href="https://alsnewstoday.com/news/rescuing-levels-stmn2-potential-new-therapy-als-harvard-study/">Stathmin-2</a> (STMN2) is the protein most significantly regulated by TDP-43 in people. This protein is important for neural repair and stability, and it is abundant in motor neurons. But its levels drop significantly when TDP-43 is faulty, and stathmin-2 is known to be at <a href="https://alsnewstoday.com/news/antisense-oligonucleotide-stathmin-2-levels-lab-grown-motor-neurons-qrl-201-als-quralis/">lower-than-normal levels</a> in nearly all ALS patients.
QRL-201 is a first-in-class experimental therapy designed to raise STMN2 levels in patients. This has been shown to <a href="https://alsnewstoday.com/news/mda-2023-designer-dna-drug-als-shows-promise-early-studies/">lessen the damage caused by TDP-43 aggregates</a>, and to restore nerve cells&#8217; ability to repair damage. As such, QRL-201 could work to slow or prevent ALS progression.
ANQUR is the first trial evaluating a therapy designed to rescue STMN2 production. It aims to test the safety, tolerability, and pharmacological properties of QRL-201 in up to 64 people with ALS.
Participants will be randomly assigned to one of eight increasing doses of the therapy or to a placebo, both given by an injection into the spinal canal (intrathecal injection). Each dosing group will include eight patients, six being treated with QRL-201 and two being given a placebo. A first group in Canada is fully enrolled and dosing is underway.
The company plans to open additional sites in the U.S. and U.K.
&#8220;We believe QRL-201 has the potential to halt disease progression, which could transform the care and treatment of ALS. We are dedicated to ensuring efficient advancement of our ANQUR clinical trial so that we can fulfill our mission to make a meaningful difference in patients&#8217; lives,&#8221; Roet said.

Tag: European Union

CHMP delays opinion on masitinib, up for conditional EU approval

Phase 1 trial of QRL-201 to open for patients at sites across Europe