AB Science has optimized the design of a Phase 3 confirmatory study for mastinib, its oral treatment for amyotrophic lateral sclerosis (ALS), to avoid any possibility of bias. The optimized protocol for the study (NCT03127267), not yet recruiting, was validated by the European Medicines Agency (EMA).
Although AB Science has generated new data to address major objections raised by the EMA to its previous conditional marketing authorization application for mastinib, it has not yet decided to file a new submission, the company said in a press release.
Masitinib is designed to lessen the symptoms of ALS by targeting proteins called tyrosine kinases, which play a role in the inflammatory process. A tyrosine kinase inhibitor (TKI), masitinib blocks the action of immune cells called mast cells and microglia, which promote neurodegeneration.
AB Science applied to the EMA for conditional marketing authorization for masitinib for ALS in October 2016. The application was filed after masitinib met its primary end goal of improving the functioning of ALS patients in a Phase 2/3 AB10015 clinical trial (NCT02588677). That trial tested the effectiveness and safety of masitinib combined with Rilutek (riluzole) versus that of Rilutek and placebo.
The EMA issued a negative opinion on the application in April 2018, based on low reliability and robustness of the data, and possible bias in the primary analysis. Soon after the decision, the company opted not to apply for re-examination, and instead focus on generating new data to file a new, more robust application.
AB Science said in a recent web conference that new data it had generated addressed the major objections raised by the EMA. However, the company has not yet decided to start a new submission.
The company also announced that it had optimized the design of a Phase 3 confirmatory study, to avoid any possibility of bias.
The optimized protocol was revised and validated by the EMA, and will include patients at more stages of the disease, specifically those with mildly severe ALS. The protocol also modifies the dose of masitinib between 3 and 6 mg/kg/day, according to the response of each participant, to reduce the number of drop-outs due to tolerance issues.
The study will enroll 500 participants across 50 medical centers specialized in ALS, and evaluate changes in the revised ALS functional rating scale (ALSFRS-R) — measuring abilities such as walking, speech, hand control, and breathing — after approximately four months of treatment. The study is expected to begin during the second half of 2019.
AB Science also announced that the Agence Nationale de sécurité du Médicament et des produits de santé (ANSM) — the French agency that assesses the benefits and risks associated with the use of health products — lifted its decision to suspend the company’s clinical trials. It is now back to the regular authorization process.
The company highlighted the importance of seeking approval for new ALS therapies.
“There is still a high need for new treatments in ALS. In Europe, there has been no drug registered since Riluzole 32 years ago,” the company said.