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The developer of the add-on treatment <a href="https://alsnewstoday.com/masitinib/">masitinib</a> for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) has been given the go-ahead to ask Health Canada to reconsider its decision from earlier this year against the approval of the oral therapy.
The Canadian regulatory agency granted reconsideration eligibility to <a href="https://www.ab-science.com/">AB Science</a> for masitinib — meaning the company now has 45 days to file a new request seeking the drug&#8217;s approval.
AB Science already has met with Health Canada to discuss the reconsideration process, the company announced in a <a href="https://www.globenewswire.com/news-release/2024/04/03/2857229/0/en/AB-Science-announces-that-Health-Canada-has-granted-eligibility-for-reconsideration-request-for-masitinib-in-ALS.html">press release</a>. As part of the reconsideration, new assessors will re-examine the approval decision based on available data. This could take up to six months.
&#8220;The pivotal argument is on the treatment of missing data,&#8221; AB Science stated in the release, noting that analyses show the therapy was &#8220;successful&#8221; in earlier research.
[recommended-reading id=81693]
<h3>Masitinib tested in nearly 400 ALS patients in Phase 3 trial</h3>
AB first <a href="https://alsnewstoday.com/news/masitinib-under-review-als-add-on-therapy-canada/">asked Health Canada to approve masitinib</a> in 2022. However, the agency <a href="https://alsnewstoday.com/news/health-canada-more-masitinib-data-stops-review/">paused its review</a> after a few months, citing a need for more information. The review was then <a href="https://alsnewstoday.com/news/health-canada-less-than-7-months-decide-approval-masitinib/">resumed in 2023</a> after a revised application was submitted, but the agency decided in February to <a href="https://alsnewstoday.com/news/als-oral-therapy-masitinib-rejected-health-canada/">reject that request</a>.
Less than a month earlier, regulators in the European Union had <a href="https://alsnewstoday.com/news/chmp-delays-opinion-conditional-eu-approval-masitinib-als/">delayed their decision on masitinib</a>, which now is likely by June.
Masitinib is an oral therapy designed to block enzymes that drive inflammation and nerve cell death in ALS. It&#8217;s being investigated as an add-on treatment to riluzole (sold as <a href="https://alsnewstoday.com/rilutek-riluzole-for-als/">Rilutek</a> among others), the only therapy proven to date to slow disease progression and extend survival in people with the neurodegenerative condition.
&#8220;The recent failure of numerous phase 2 or 3 programs … have dashed the community&#8217;s hopes of benefiting from new therapeutic advances and have effectively set us back with riluzole being the only treatment with a proven modest effect in the overall ALS population,&#8221; said Albert Ludolph, MD, PhD, principal investigator of the Phase 3 trial that tested masitinib, and also medical director of the neurology department at the University of Ulm, in Germany.
&#8220;We should learn from [these] failures,&#8221; Ludolph added.
AB Science&#8217;s applications were supported by data from the <a href="https://clinicaltrials.gov/ct2/show/NCT02588677">AB10015 Phase 3 trial (NCT02588677)</a>, in which 394 ALS patients were randomly assigned one of two doses of masitinib (3 or 4.5 mg/kg) or a placebo, given on top of the standard ALS medication Rilutek.
Data showed that the higher masitinib dose significantly outperformed the placebo at <a href="https://alsnewstoday.com/news-posts/2019/07/10/add-on-masitinib-slows-progression-of-als-final-phase-2-3-trial-results-show/">slowing physical decline</a>, as indicated by a 27% reduction in ALS Functional Rating Scale-Revised (ALSFRS-R) scores after one year.
These benefits were seen in patients with disease progression deemed normal, meaning an ALSFRS-R decrease of less than 1.1 points a month. Slower declines in lung function and quality of life also were found for these patients.
Overall, however, data showed that normal progressors with <a href="https://alsnewstoday.com/news/als-therapy-masitinib-works-best-add-on-moderate-disease-analysis/">mild or moderate ALS</a> achieved the best outcomes, with masitinib slowing the rate of disease progression by 42% and extending survival by 25 months, or just longer than two years.
[recommended-reading id=38613]
<h3>Health Canada had cited 3 issues with data from key AB10015 studt</h3>
Health Canada nevertheless rejected AB&#8217;s application, citing three limitations to the available AB10015 data.
First, the year-long study generated a great deal of missing data. To impute, or represent, these missing values, the researchers used certain statistical tests — but the agency said the resulting data could have biased the results and made masitinib appear more effective than it was.
According to AB, however, sensitivity analyses continued to support masitinib&#8217;s efficacy when the missing data were considered a placebo, a recognized conservative approach to dealing with missing data. Rerandomization, for more precise estimates of causal effects, also was successful.
&#8220;A 48-week study inevitably generates a large number of missing data,&#8221; Ludolph said, who noted that &#8220;this situation is not unique to masitinib.&#8221;
&#8220;Masitinib has published results over a 48-week period, positive when appropriate methodology to treat missing data is applied, and it deserves careful consideration,&#8221; Ludolph said.
Second, after AB10015 was completed, the developer created a new subgroup of study individuals it dubbed &#8220;patients with ALS prior to any loss of function.&#8221;
Among these patients, masitinib significantly extended overall survival versus the placebo. However, the agency said this finding was unreliable because this subgroup wasn&#8217;t part of the study&#8217;s original design.
In its release, AB noted that the subgroup, defined based on masitinib&#8217;s mechanism of action, had a significant median overall survival benefit of more than 22 months, or nearly two years, which was unlikely to be artificial because all patients had access to the same care.
[quote=&#8221;center&#8221;]Masitinib has published results over a 48-week period, positive when appropriate methodology to treat missing data is applied, and it deserves careful consideration.[/quote]
Health Canada&#8217;s third issue was late-in-the-trial changes to the study protocol that were not sufficiently justified, undermining the data&#8217;s reliability. While AB previously acknowledged that the protocol changes were not data-driven, the company said they were typical for such a large clinical trial.
Further, the company also stated that there was a near significant change in the secondary outcome of the Combined Assessment of Function and Survival (CAFS), a composite measure of survival-based outcomes and ALSFRS-R decline. This occurred despite the study not being statically powered for this outcome.
Lastly, progression-free survival, the time from the study&#8217;s start to the earliest date of a functional decline of at least nine ALSFRS-R points, did show significant improvement in favor of masitinib, according to AB Science.

Health Canada agrees to reconsider request for masitinib approval

Health Canada is now reviewing <a href="https://alsnewstoday.com/ionis-sod1-rx-biib067/">Qalsody</a> (tofersen) as a potential treatment for people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) who carry mutations in the SOD1 gene, according to the therapy&#8217;s developer <a href="https://www.biogen.com/">Biogen</a>.
The Canadian regulatory authority agreed to review Biogen&#8217;s application for the therapy&#8217;s approval, with its decision expected in early 2025, according to a <a href="https://www.newswire.ca/news-releases/health-canada-accepts-for-review-new-drug-submission-for-tofersen-for-treatment-of-rare-genetic-form-of-als-806869519.html">company press release</a>.
If approved, Qalsody will become the first and only therapy approved in Canada to target a genetic cause of ALS. Qalsody already is <a href="https://alsnewstoday.com/news/fda-approves-tofersen-now-qalsody-treatment-adults-sod1-als/">approved in the U.S.</a> and has been <a href="https://alsnewstoday.com/news/committee-favors-eu-approval-qalsody-1st-treatment-sod1-als/">recommended for approval</a> in the European Union to treat ALS-SOD1 patients.
The application &#8220;represents a critical milestone for the Canadian ALS community and those suffering from this ultra-rare genetic form of the disease that robs them of time with loved ones,&#8221;said Eric Tse, vice president and general manager of Biogen Canada.
&#8220;For over a decade, Biogen has been committed to advancing ALS research to provide a deeper understanding of this devastating disease. We are passionate about doing what we can to make a difference and are deeply committed to the rare disease community,&#8221; Tse added.
[recommended-reading id=79512]
<h3>Request for approval based on data from VALOR trial</h3>
Mutations in the SOD1 gene are found in as many as 20% of people with <a href="https://alsnewstoday.com/forms-of-als-familial-als/">familial ALS</a> and in up to 2% of <a href="https://alsnewstoday.com/sporadic-als/">sporadic ALS</a> cases. These mutations lead to the production of an abnormal SOD1 protein, which tends to accumulate and form toxic clumps inside nerve cells, causing damage.
Qalsody belongs to a class of therapies called antisense oligonucleotides, or ASOs. Such therapies prevent the production of disease-causing proteins by interfering with their messenger RNA (mRNA) — an intermediate molecule derived from DNA that&#8217;s used as a template for protein production.
The drug is designed to bind to SOD1&#8217;s mRNA and target it for degradation, preventing the cell&#8217;s protein-making machinery from reading this template to produce the protein. This causes a marked reduction in SOD1 levels, which is expected to slow disease progression and extend survival.
The treatment is administered via intrathecal injection, or an injection into the spinal canal. In the U.S., it&#8217;s given as three initial three doses 14 days apart, followed by maintenance doses every 28 days.
Qalsody&#8217;s submission to Health Canada was based on data from Part 3 of the <a href="https://clinicaltrials.gov/study/NCT02623699">VALOR trial (NCT02623699)</a>, which enrolled 108 adults with ALS and a confirmed SOD1 mutation. It aimed to assess the safety and efficacy of Qalsody versus a placebo.
Participants were randomly assigned to receive eight intrathecal injections of either 100 mg of Qalsody or a placebo over six months.
The trial&#8217;s main goal was to assess changes in functional disability, as measured with the ALS Functional Rating Scale-Revised (ALSFRS-R), in a group of 60 patients with fast-progressing disease after about seven months.
That goal <a href="https://alsnewstoday.com/news/phase-3-tofersen-trial-fails-slow-sod1-als-trends-hopeful-valor-trial/">was not met</a>, but there were some indications that Qalsody slowed the decline in measures of lung function and muscle strength. Also, the treatment <a href="https://alsnewstoday.com/news/early-tofersen-treatment-may-slow-sod1-progression-valor-study/">significantly reduced</a> spinal fluid levels of SOD1 and blood levels of neurofilament light chain (NfL), a marker of nerve cell degeneration, both of which increased in the placebo group.
After completing the trial, 95 participants joined an <a href="https://clinicaltrials.gov/study/NCT03070119">open-label extension study (NCT03070119)</a>, in which all are receiving Qalsody for up to seven years. That study is expected to be concluded in June.
After one year, data from the Phase 3 study and its extension showed that patients who were always on Qalsody experienced a smaller drop in their ALSFRS-R scores relative to those who were initially assigned to the placebo and then switched to the treatment in the extension study. That decline averaged six points for those always treated versus 9.5 points for patients who switched from the placebo.
The early-start group also showed significant extensions in survival and in time to death or permanent ventilation.
A Phase 3 trial called <a href="https://clinicaltrials.gov/study/NCT04856982">ATLAS (NCT04856982)</a>, launched in 2021, is now testing whether Qalsody can delay the onset of disease symptoms in individuals with a SOD1 mutation who already show signs of neuronal damage —  specifically, who have elevated blood levels of NfL — but are asymptomatic.
The trial, slated to run through 2027, is expected to involve about 150 patients who receive the treatment or a placebo for up to two years. Top-line data also is anticipated in 2027.

Health Canada now reviewing Qalsody as treatment for SOD1-ALS

Health Canada has issued a notice of noncompliance-withdrawal saying it won&#8217;t approve the oral therapy <a href="https://alsnewstoday.com/masitinib/">masitinib</a> as an add-on treatment for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
Its developer, <a href="https://www.ab-science.com/">AB Science</a>, can submit a request for reconsideration within the next month, which it plans to do, it announced in a <a href="https://www.globenewswire.com/news-release/2024/02/26/2835372/0/en/AB-Science-announces-that-Health-Canada-has-issued-a-Notice-of-Non-Compliance-Withdrawal-NON-w-for-masitinib-in-ALS.html">press release</a>. As part of a reconsideration, which could take up to six months, new assessors will re-examine the decision based on available data.
AB first sought <a href="https://alsnewstoday.com/news/masitinib-under-review-als-add-on-therapy-canada/">Health Canada&#8217;s approval</a> in 2022, but the <a href="https://alsnewstoday.com/news/health-canada-more-masitinib-data-stops-review/">review was paused</a> after a few months because the regulatory agency said it needed more information from AB. Health Canada <a href="https://alsnewstoday.com/news/health-canada-less-than-7-months-decide-approval-masitinib/">resumed its review</a> in May 2023 after a revised application was submitted.
The rejection comes less than a month after authorities in Europe <a href="https://alsnewstoday.com/news/chmp-delays-opinion-conditional-eu-approval-masitinib-als/">delayed a ruling on masitinib</a>.
The oral therapy is designed to block enzymes that drive inflammation and nerve death in ALS, which is expected to slow disease progression.
[recommended-reading id=81407]
<h3>Outcomes of Phase 2/3 clinical trial</h3>
AB’s applications are based mainly on data from a Phase 2/3 clinical trial called <a href="https://clinicaltrials.gov/ct2/show/NCT02588677">AB10015 (NCT02588677)</a>. The study enrolled 394 people with ALS who were given one of two doses of masitinib (3 or 4.5 mg/kg) or a placebo as an add-on to the approved treatment <a href="https://alsnewstoday.com/als-treatment/rilutek-riluzole/">Rilutek</a> (riluzole).
After nearly a year, the rate of disease progression — measured by the ALS Functional Rating Scale Revised or ALSFRS-R — was <a href="https://alsnewstoday.com/news-posts/2019/07/10/add-on-masitinib-slows-progression-of-als-final-phase-2-3-trial-results-show/">27% slower</a> in those given the higher masitinib dose over a placebo.
This was observed in the patients with “normal” disease progression, defined as an ALSFRS-R decline of less than 1.1 points a month, who also had significantly slower declines in lung function and quality of life.
The greatest benefits, however, were seen in normal progressors <a href="https://alsnewstoday.com/news/als-therapy-masitinib-works-best-add-on-moderate-disease-analysis/">with mild or moderate ALS</a>. In these patients, masitinib slowed the rate of disease progression by 42% and extended survival by 25 months.
<h3>The basis for rejecting masitinib</h3>
In its notice, Health Canada highlighted three issues with the available data from the AB10015 study. First, the agency said changes in the study protocol were made late in the trial and weren&#8217;t sufficiently justified, leading to uncertainty about how reliable the results are. Second, the agency expressed concern that some statistical tests used to account for missing data could have biased the results, making it seem like masitinib was more effective than it really was.
In its press release, AB acknowledged that changes to the protocol were not data-driven and that they were within the normal range for a large clinical trial. The company also argued that many different statistical tests to account for missing data consistently indicate a clinical effect of masitinib.
The third issue raised by Health Canada is that, as part of its application, AB defined a new subpopulation of ALS patients, namely &#8220;patients with ALS prior to any loss of function.&#8221; In this subpopulation, overall survival was extended with masitinib compared to a placebo, but Health Canada said this finding isn&#8217;t reliable because the subgroup was defined after the study was already over, rather than being considered as part of its original design.
AB said the subpopulation was defined based on guidelines from European regulators and is logical given the push to start treating ALS as soon as possible. The company said improvements in overall survival seen in this subgroup are unlikely to be artificial because all the patients had access to the same supportive care, except that some were given masitinib and others got a placebo.
These counterarguments will form the basis of AB&#8217;s request for reconsideration, the company said.
The company is also conducting a global <a href="https://clinicaltrials.gov/ct2/show/NCT03127267">Phase 3 clinical trial (NCT03127267)</a> to further support masitinib as an add-on treatment to Rilutek. The study will include 495 participants with mild to moderate ALS who were diagnosed less than two years before screening. They will receive daily masitinib (4.5 or 6 mg/kg) or a placebo for nearly a year while continuing Rilutek.

Health Canada rejects masitinib application; reconsideration sought

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.
[recommended-reading id=21684]
<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.
[recommended-reading id=83581]
<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.ab-science.com/" rel="nofollow">AB Science</a> has submitted its response to the European Medicines Agency (EMA), part of an ongoing review process aiming for the conditional approval of <a href="https://alsnewstoday.com/masitinib/">masitinib</a> as an add-on oral therapy for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The Committee for Medicinal Products for Human Use (CHMP), an arm of the EMA, will assess the answers to questions it had following an initial 120-day review. CHMP then is expected to make a recommendation regarding masitinib&#8217;s conditional approval.
Responses to questions from Health Canada, where the investigative therapy is also under review for conditional approval, will be filed by their April 12 deadline, AB Science said in a <a href="https://www.globenewswire.com/news-release/2023/04/04/2641085/0/en/AB-Science-announces-that-it-has-submitted-its-response-to-the-day-120-questions-in-the-EMA-regulatory-review-of-masitinib-in-amyotrophic-lateral-sclerosis-and-clarifies-the-new-ti.html">company press release</a>. The Canadian regulatory agency <a href="https://alsnewstoday.com/news/health-canada-more-masitinib-data-stops-review/">paused its review of masitinib</a>, asking for more supporting information, late last year.
Conditional approval is given to medicines that fulfill an unmet medical need and whose preliminary benefits outweigh their potential risks. If granted, masitinib will be marketed in Europe under the brand name Alsitek. The therapy&#8217;s full approval requires verification in confirmatory clinical trials.
[recommended-reading id=82931]
<h3>Masitinib tested in combination with Rilutek (riluzole)</h3>
&#8220;The European regulation has provided since 2004 a legislative framework … to support the conditional registration of drugs in incurable diseases when definitive evidence of efficacy is not yet fully met,&#8221; said Sabine Turgeman, executive director of the <a href="https://www.arsla.org/">Association pour la recherche sur la SLA </a>.
&#8220;Conditional registration is the right procedure to accelerate access of new treatments to patients. We urge the EMA to apply maximum regulatory flexibility in the context of ALS, an incurable and fatal degenerative disease,&#8221; Turgeman added.
&#8220;Canadian families living with the devastating disease of ALS and in urgent need of new drug therapies want masitinib to benefit from this conditional registration,&#8221; said Bre Hamilton, executive director of <a href="https://alsactioncanada.org/">ALS Action Canada</a>.
Masitinib is designed to suppress the activity of select tyrosine kinases, enzymes that modulate the function of certain immune cells that drive inflammation in ALS. As such, it is expected to help slow disease progression and ease <a href="https://alsnewstoday.com/symptoms-of-als/">ALS symptoms</a>.
The therapy was evaluated in the <a href="https://clinicaltrials.gov/ct2/show/NCT02588677">Phase 2/3 clinical trial (NCT02588677)</a>, called AB10015, as an add-on treatment to <a href="https://alsnewstoday.com/rilutek-riluzole-for-als/">Rilutek</a> (riluzole), an approved ALS therapy. Its 394 enrolled patients were randomly assigned to one of two daily masitinib doses (3 or 4.5 mg/kg) or to a placebo, in combination with Rilutek, for about 11 months (48 weeks).
AB10015 met its primary <a href="https://alsnewstoday.com/news/clincal-trial-shows-masitinib-improves-functioning-of-als-patients/">goal of functional gains</a> in masitinib-treated patients, the company reported in 2017. Although the trial did not finish until 2018 and all data was not available for analyses, AB Science asked for masitinib&#8217;s conditional approval in Europe based on interim results.
<a href="https://alsnewstoday.com/news/ema-issues-negative-opinion-masitinib-conditional-marketing-authorization/">CHMP issued a negative opinion</a>, not supporting conditional approval, in 2018, and the company decided <a href="https://alsnewstoday.com/news/ab-science-not-pursuing-ema-reexamination-marketing-approval-masitinib-als-treatment/">not to pursue further</a> an EMA application at that time.
Its recent <a href="https://alsnewstoday.com/news/masitinib-again-under-review-eu-potential-als-treatment/">EMA application for masitinib</a>, accepted in 2022, includes final trial results, demonstrating that Rilutek plus masitinib at its higher dose <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</a> in patients with “normal” disease progression by 27% compared with Rilutek alone, meeting the study&#8217;s main efficacy goal. Reasonable safety also was found.
Normal disease progression was defined as a monthly decline in ALS Functional Rating Scale–Revised (ALSFRS-R) scores of less than 1.1 points. The combination therapy also slowed declines in quality of life and lung function in patients randomized to masitinib at 4.5 mg/kg daily.
<h3>Ongoing Phase 3 trial aims to confirm benefits reported in earlier study</h3>
In the overall trial population, no significant differences were observed in survival. Median overall survival was 37 months for patients on Rilutek alone and 33 months for those also given masitinib.
But after adjusting the analysis to include only patients with mild or moderate disease — those with at least two points or higher on every ALSFRS-R item at the study’s start — researchers found significant survival benefits.
In this group, patients on masitinib lived for a median of 69 months, compared with 44 months for those on a placebo. This resulted in a median survival difference of 25 months, representing a 44% reduction in the risk of death.
AB Science now aims to confirm the combination&#8217;s benefits in AB19001, an ongoing and global <a href="https://clinicaltrials.gov/ct2/show/NCT03127267">Phase 3 clinical trial (NCT03127267)</a>. It is enrolling or has enrolled up to 495 adults diagnosed within the last two years with normal ALS progression and mild to moderate disease.
Participants are randomized to Rilutek in combination with either masitinib, at a daily dose of 4.5 or 6 mg/kg, or a placebo for 48 weeks.
The trial&#8217;s main goal is to determine whether masitinib slows disease progression based on ALSFRS-R score declines over those weeks. Secondary goals include changes in quality of life, lung function, and muscle strength, a combined assessment of function and survival, and time to disease progression or death. Top-line data is expected later this year.
&#8220;Masitinib is one of the most promising drugs in ALS that has just been submitted to the EMA conditional approval process,&#8221; said Olivier Goy, co-founder and president of October, a European finance company. &#8220;I strongly support drugs that are submitted for conditional approval, especially when they have complementary mechanisms of action.&#8221;

Tag: Health Canada

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