The European Medicines Agency (EMA) has agreed to review an application seeking the conditional approval of AB Science’s masitinib, now Alsitek, for the treatment of amyotrophic lateral sclerosis (ALS).
Conditional approval is granted to a medication whose immediate availability fulfills an unmet medical need, when its preliminary benefits are found to outweigh its potential risks. In these cases, the therapy’s full approval depends on further verification of its clinical benefits in confirmatory trials.
Alsitek is an oral therapy designed to reduce the activity of several immune cells involved in neuroinflammation and neurodegeneration by suppressing an enzyme called tyrosine kinase. This is expected to slow disease progression in ALS and other neurodegenerative diseases.
Previous trial data showed that Alsitek, when added to the approved ALS therapy Rilutek (riluzole), significantly slows disease progression and prolongs survival in people diagnosed with ALS.
“ALS is a devastating disease and there is a tremendous need for new treatments that can improve the life of the patients to be available as soon as possible,” Alain Moussy, AB Science’s CEO and co-founder, said in a company press release.
“AB Science is committed to deliver a new disease modifying treatment to the ALS community, a drug that can change the perspective of the patients in the long run,” Moussy added.
The review process, which has already started, will be conducted by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The committee’s opinions are generally accepted by the European Commission, which makes final decisions on therapy approval for the 27 members of the European Union. A decision is expected within about seven months.
This marks the second time AB Science has filed for Alsitek’s conditional approval in Europe. The first — submitted in 2016 and based on interim results from the AB10015 Phase 2/3 trial (NCT02588677) — received a CHMP negative opinion in 2018.
At the time, the company decided not to seek re-examination of the application because it would not be allowed to present new data during this process — which would make it impossible to address all the issues raised by the committee.
Now, the re-submitted application contains final results from the trial, which ended in March 2018, and additional efficacy and survival analyses, as well as further preclinical data on the therapy’s mechanism of action. These data were presented and accepted for filing in a pre-submission meeting with the CHMP rapporteur, who is a committee member leading the evaluation of an application.
A similar application is also being reviewed by health authorities in Canada, with a decision likely expected by year’s end.
“AB Science will continue to work closely with all agencies in the world to deliver masitinib to patients in an optimal regulatory pathway,” Moussy added.
What was the purpose of the AB10015 Phase 2/3 trial?
The AB10015 Phase 2/3 trial evaluated the safety and effectiveness of nearly one year of treatment with Rilutek plus Alsitek — at a daily dose of 3 mg/kg or 4.5 mg/kg — against Rilutek alone, in 394 ALS patients.
Final data showed that Rilutek plus Alsitek’s higher dose significantly slowed disease progression (by 27%) compared with standard therapy alone among patients with normal disease progression — meeting the trial’s main efficacy goal.
The new application also contains additional analyses for this main goal: one imputing all missing data from patients who discontinued treatment early, and another imputing missing data with a penalty for those who discontinued Alsitek for lack of efficacy or toxicity.
The results remained significant, with all demonstrating the superiority of the Rilutek-Alsitek combo over Rilutek alone at slowing disease progression.
Long-term survival data also included patients with moderate ALS, “which corresponds to selection of ALS patients early in the course of their disease and is also consistent with newly diagnosed patients,” AB Science stated in the release.
Results from this analysis showed that patients receiving Alsitek’s higher dose lived for two more years that those on standard therapy alone — reflecting a significant 44% lower risk of death.
The therapy was generally safe, and “a remonitoring of all efficacy and safety data and a complete reassessment of the Alsitek safety database” was also provided in the application, the company stated.
AB Science is now confirming the therapy’s benefits in the larger international Phase 3 AB19001 trial (NCT03127267), which seeks to enroll up to 495 adults diagnosed with ALS in the past two years and who show normal progression and mild to moderate functional impairments.
After a pause due to heart-related safety concerns, patient enrollment was resumed with changes in protocol that include closer monitoring of heart health.