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Health Canada has resumed its review of <a href="https://www.ab-science.com/">AB Science</a>’s application seeking approval of <a href="https://alsnewstoday.com/masitinib/">masitinib</a>, an oral add-on therapy for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), after the agency halted its review late last year.
In 2022, the agency <a href="https://alsnewstoday.com/news/masitinib-under-review-als-add-on-therapy-canada/">agreed to review</a> the application under the notice of compliance with conditions (NOC/c) policy, which would allow the therapy to receive conditional approval and gain early market access.
However, the <a href="https://alsnewstoday.com/news/health-canada-more-masitinib-data-stops-review/">review was discontinued</a> a few months later when Health Canada issued a notice of deficiency for the application, meaning more information on the therapy was needed from the company within 90 days.
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<h3>AB Science submitted revised application in April</h3>
In April, AB Science submitted its revised application, which was screened and found acceptable for the review process to continue. Under the NOC/c policy, Health Canada now has no more than 200 days, or about seven months, to decide whether to approve masitinib.
&#8220;There is an urgent need expressed by ALS patients and their families in Canada to access masitinib treatment under NOC/c status and we will continue to work diligently with Health Canada to respond to this need,&#8221; Alain Moussy, AB Science&#8217;s co-founder and CEO, said in a <a href="https://www.globenewswire.com/news-release/2023/05/09/2664790/0/en/AB-Science-announces-that-Health-Canada-has-resumed-its-review-of-the-New-Drug-Submission-for-masitinib-in-amyotrophic-lateral-sclerosis-following-issuance-of-a-screening-acceptanc.html">company press release</a>.
Masitinib is also undergoing review for conditional approval in Europe, with a recommendation from Europe&#8217;s Committee for Medicinal Products for Human Use <a href="https://alsnewstoday.com/news/ema-given-responses-masitinib-conditional-approval-review/">expected in the next few months</a>.
In people with ALS, the nerve cells that control voluntary movements, called motor neurons, progressively die, leading to <a href="https://alsnewstoday.com/als-symptoms/">symptoms</a> such as muscle atrophy and wasting. Motor neuron loss is known to be driven by inflammation caused by the activity of certain immune cells, including macrophages, neutrophils, and mast cells.
Masitinib is designed to suppress the activity of tyrosine kinase, an enzyme essential for the function of these immune cells, with the goal of slowing disease progression in ALS and other neurodegenerative diseases.
[quote=&#8221;center&#8221;]There is an urgent need expressed by ALS patients and their families in Canada to access masitinib treatment under NOC/c [notice of compliance with conditions] status and we will continue to work diligently with Health Canada to respond to this need.[/quote]
<h3>Phase 2/3 trial shows slower disease progression in patients on masitinib</h3>
Approval applications were supported by final data from the <a href="https://clinicaltrials.gov/ct2/show/NCT02588677">AB10015 Phase 2/3 clinical trial (NCT02588677)</a>, which evaluated masitinib as an add-on to the approved ALS therapy <a href="https://alsnewstoday.com/als-treatment/rilutek-riluzole/">Rilutek</a> (riluzole) in 394 ALS patients. Participants were assigned to one of two masitinib doses (3 or 4.5 mg/kg) or a placebo.
After 48 weeks (about 11 months) of daily therapy, <a href="https://alsnewstoday.com/news-posts/2019/07/10/add-on-masitinib-slows-progression-of-als-final-phase-2-3-trial-results-show/">disease progression was significantly slowed by 27%</a> in patients taking the 4.5 mg/kg dose of masitinib plus Rilutek compared with Rilutek and a placebo.
AB Science&#8217;s revised application contained a new examination of AB10015 data showing that patients with mild or moderate disease severity <a href="https://alsnewstoday.com/news/als-therapy-masitinib-works-best-add-on-moderate-disease-analysis/">benefited the most from masitinib</a>.
This analysis focused on patients who had yet to experience a complete loss of any physical function, defined as a zero score on any of the 12 items on the ALS Functional Rating Scale-Revised (ALSFRS-R). This subgroup accounted for about 80% of participants in AB10015.
According to the new data, there was a significant 18.4% improvement in the combined assessment of function and survival (CAFS) in people receiving daily 4.5 mg/kg masitinib compared with those given a placebo alone.
CAFS is a composite outcome that ranks patients&#8217; clinical outcomes based on survival time and rate of ALSFRS-R decline. It is now recommended by Health Canada and the U.S. Food and Drug Administration as a primary measure to assess efficacy in ALS trials.
Masitinib also significantly slowed overall disease progression, based on ALSFRS-R scores, and the decline in lung function and quality of life.
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<h3>Ongoing AB19001 Phase 3 trial testing if masitinib can slow ALSFRS-R declines</h3>
AB Science is now confirming the findings in the ongoing <a href="https://clinicaltrials.gov/ct2/show/NCT03127267">AB19001 Phase 3 clinical trial (NCT03127267)</a>, which aims to enroll up to 495 adults with mild to moderate ALS who were diagnosed in the prior two years.
Like the AB10015 study, participants will be assigned to one of two masitinib daily doses (4.5 or 6 mg/kg) or a placebo, given in combination with Rilutek, for 48 weeks.
Whether masitinib can slow ALSFRS-R declines is AB19001&#8217;s main goal. CAFS scores, and changes in muscle strength, lung function, quality of life, as well as time to disease progression or death, will also be assessed. The company expects to report top-line data this year.
Masitinib has been granted orphan drug status in the U.S., the European Union, and, more recently, <a href="https://alsnewstoday.com/news/als-therapy-masitinib-gains-orphan-drug-status-switzerland/">Switzerland</a>, a designation given to potential treatments for life-threatening or chronic rare diseases.

Health Canada resumes its review of add-on ALS therapy masitinib

<a href="https://www.amylyx.com/">Amylyx Pharmaceuticals</a> is facing a new hurdle — a second round of questions from a European Medicines Agency (EMA) committee — in its quest to have <a href="https://alsnewstoday.com/amx0035/">AMX0035</a> approved as a treatment for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) in Europe.
The questions, from the Committee for Medicinal Products for Human Use, known as CHMP, come after the company completed a scientific advisory group meeting, in which experts come together to evaluate a specific drug and provide recommendations for approval. However, the committee said there were still certain major objections to AMX0035 that should be addressed.
Amylyx will now respond to the questions, and expects an opinion from the committee by mid-2023. The EMA will consider that opinion in its decision on AMX0035&#8217;s potential approval.
While the company had previously said it was expecting a decision from the regulatory authority <a href="https://alsnewstoday.com/news/phoenix-trial-approved-als-therapy-relyvrio-amx0035-enrolled/">in the first half of 2023</a>, updated timelines now point to &#8220;the third quarter of 2023 at the earliest,&#8221; Amylyx stated in <a href="https://www.businesswire.com/news/home/20230313005731/en/Amylyx-Pharmaceuticals-Reports-Fourth-Quarter-and-Full-Year-2022-Financial-Results">press release</a> announcing its financial results for 2022.
“We continue to engage with the European Medicines Agency as it reviews our marketing authorisation application for AMX0035,&#8221; said Joshua Cohen and Justin Klee, co-CEOs at Amylyx. &#8220;We remain focused on our efforts &#8230; to drive the broadest coverage possible for this important new therapeutic option.”
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<h3>&#8216;Much work remains,&#8217; Amylyx CEOs say</h3>
AMX0035 is an oral fixed-dose combination of two small molecules — tauroursodeoxycholic acid and sodium phenylbutyrate — that protect nerve cells from damage induced by cellular stress.
The treatment is <a href="https://alsnewstoday.com/news/amx0035-albrioza-oral-als-therapy-available-canada/">commercially available</a> to treat people with ALS in Canada, under the name Albrioza. In the U.S., it was <a href="https://alsnewstoday.com/news/relyvrio-amx0035-approved-us-als-treatment/">approved in September</a> of last year and is marketed as Relyvrio.
“2022 was an exceptionally exciting year for Amylyx, culminating with the approval of Relyvrio in the U.S. following the approval with conditions for Albrioza in Canada, marking an important step toward delivering much-needed advancements in treatment options to the ALS community,” Cohen and Klee said.
Approvals of AMX0035 in North America were supported by data from <a href="https://clinicaltrials.gov/ct2/show/NCT03127514">CENTAUR (NCT03127514)</a>, a Phase 2 trial in which the therapy was found to significantly slow functional decline and extend survival in people with the neurodegenerative disease. That trial involved 137 people with recently diagnosed and rapidly progressing ALS.
Now, the company is conducting the <a href="https://clinicaltrials.gov/ct2/show/NCT05021536">PHOENIX Phase 3 trial (NCT05021536)</a> to test the therapy in a larger group of patients. <a href="https://alsnewstoday.com/news/phoenix-trial-approved-als-therapy-relyvrio-amx0035-enrolled/">Enrollment was completed</a> last month, with a total of 664 participants who will receive the medication or a placebo for 48 weeks (nearly one year).
The trial’s main goals are to assess AMX0035&#8217;s safety and changes in disease progression, as measured with the ALS Functional Rating Scale-Revised (ALSFRS-R). Secondary measures include changes in lung function, quality of life, and survival.
After completing the trial, patients will be able to join an open-label extension part and continue receiving treatment for two more years.
[quote align=&#8221;center&#8221;]2022 was an exceptionally exciting year for Amylyx, culminating with the approval of Relyvrio in the U.S. following the approval with conditions for Albrioza in Canada, marking an important step toward delivering much-needed advancements in treatment options to the ALS community.[/quote]
Earlier this year, Amylyx entered an <a href="https://alsnewstoday.com/news/amylyx-select-neopharm-market-amx0035-middle-east/">exclusive license and distribution agreement</a> with <a href="https://www.neopharmisrael.co.il/">Neopharm</a>, which, pending its approval, would make the Israel-based company responsible for regulatory submissions and commercialization of AMX0035 in certain Middle East regions. Those regions include Israel, Gaza, the West Bank, and the Palestinian Authority.
“Our commercial launch is off to a strong start, and we are encouraged by the engagement we have seen from physicians, people living with ALS, and payors,” Cohen and Klee said.
“While we are thrilled with this progress, we are also cognizant that much work remains to meet our goal of quick and efficient access for every eligible person living with ALS,” they added.

Tag: regulatory review

Health Canada resumes its review of add-on ALS therapy masitinib

European approval of AMX0035 for ALS faces new hurdle in review