CHMP delays opinion on masitinib, up for conditional EU approval
EMA committee's view of ALS add-on therapy likely by June
A European Medicines Agency (EMA) committee again has delayed issuing an opinion on whether to grant conditional approval to masitinib, a potential add-on oral therapy for amyotrophic lateral sclerosis (ALS).
AB Science, the therapy’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’s application requesting masitinib’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 company press release.
New EMA guidelines were the cause of initial delayed opinion for masitinib
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 more time to review masitinib production processes 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’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 disease symptoms.
AB Science’s application is supported by the results of the Phase 2/3 AB10015 clinical trial (NCT02588677), which tested masitinib as an add-on to the approved ALS therapy Rilutek (riluzole) in 394 patients.
Findings showed that a 4.5 mg/kg daily dose of masitinib plus riluzole significantly slowed disease progression by 27% 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 mild or moderate ALS benefited most from adding masitinib. These patients lived more than two years longer than those on riluzole alone, representing a 44% reduction in mortality risk.
Phase 3 trial evaluating masitinib as riluzole add-on in nearly 500 patients
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 Phase 3 clinical trial (NCT03127267) 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.
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