Masitinib Improves ALS Patients’ Functioning, Clinical Trial Results Show

Masitinib met its main Phase 2 and 3 clinical trial goal of improving the functioning of amyotrophic lateral sclerosis (ALS) patients, according to its maker, AB Science SA.

The randomized, double-blind AB10015 (NCT02588677) trial compared the effectiveness and safety of a combination of masitinib and riluzole with a combination of a placebo and riluzole. Riluzole is marketed as Rilutek or Teglutik.

Masitinib was administered for 48 weeks. The 394 patients were randomized to get either a combination of 4.5 mg/kg/day of mastinib and riluzole, a combination of 3 mg/kg/day of mastinib and riluzole, or a combination of a placebo and riluzole.

The primary endpoint, or measuring stick, of the trial was the change in the patients’ revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) over the 48 weeks. The changes that the ALSFRS-R tracks over time correlate with patients’ quality of life and survival.

Progression free survival (PFS) was a secondary endpoint of the trial. Researchers defined it as a deterioration of more than nine points in a patient’s ALSFRS-R score, or the patient’s death.

Researchers did their analysis in two phases. In the first, they tested the effectiveness of 4.5 mg/kg/day of masitinib against a placebo. In the second, they compared the effectiveness of 3 mg/kg/day of masitinib with a placebo.

Patients who received 4.5 mg/kg/day of masitinib had a statistically significant change in their ALSFRS-R score by the end of the trial, compared with placebo-treated patients. That dose level also improved patients’ PFS and quality of life.

Researchers assessed quality of life by the change in patients’ Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ) score between the start and end of the trial. The self-report is a subjective patient measure of well-being.

Patients who received 3 mg/kg/day of masitinib also improved their ALSFRS, PFS, and quality of life scores, compared with placebo-treated patients, the trial results showed.

There were no new safety issues with the treatment or major adverse reactions.

The results will be presented at the European Network for the Cure of ALS (ENCALS) conference in Ljubljana, Slovenia, May 18 – 20.

“This is a very good news for the patients. These final data confirm findings from the study’s interim analysis and proves that masitinib is capable of slowing down motoneuron degenerative disease such as ALS, which is a devastating condition with an urgent unmet medical need,” AB Science’s CEO, Alain Moussy, said in a press release:

Professor Olivier Hermine, president of AB Science’s scientific committee, said that “perhaps the most impressive finding from this study is that masitinib has generated a significant difference in progression free survival with respect to the placebo treatment arm. Similar to cancer studies when PFS is significantly improved, this indicates a clear clinical benefit in favor of masitinib.”

Masitinib is a tyrosine kinase inhibitor. It targets mast cells and macrophages — which are important to immunity — by inhibiting a limited number of kinases. Masitinib is being developed to treat ALS and similar conditions, and as an inflammatory disease therapy.

In October 2016, AB Science announced that the European Union had accepted a conditional marketing authorization application for masitinib as a treatment for ALS.