French biotech company AB Science presented the results of the Phase 3 clinical trial for its lead compound masitinib, which showed effectiveness in improving the functioning of patients with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.
The randomized, double-blind clinical trial (NCT02588677) compared the efficacy and safety of combining masitinib with riluzole (Rilutek or Teglutik), also an ALS drug, with a combination of a placebo and riluzole. A total of 394 ALS patients were randomly assigned to receive either a treatment combination of 4.5 mg/kg/day of masitinib and riluzole, a combination of 3 mg/kg/day of masitinib and riluzole, or a combination of a placebo and riluzole for up to 48 weeks.
The study’s primary goal was to observe changes in participating patients’ revised ALS Functional Rating Scale (ALSFRS-R), used to monitor patients’ functional change over time. A secondary goal was to study progression free survival (PFS), which trial investigators defined as either a patient’s death or a deterioration of more than nine points in a patient’s ALSFRS-R score.
The results showed that masitinib administered at 4.5 mg/kg/day along with riluzole in ALS patients generated a therapeutic benefit when compared to placebo treatment. This masitinib dosage slowed patients’ loss of function, improved their PFS, and reduced the decline in quality of life.
Patients who received 3 mg/kg/day of masitinib also improved their ALSFRS, PFS (through delayed disease progression), and quality of life scores compared to patients receiving a placebo. The study found masitinib, which is also being tested for use in a wide range of other conditions, to be safe without causing major adverse effects.
Study results were presented at the 2017 European Network for the Cure of ALS annual meeting in Ljubljana, Slovenia, on May 18-20.
At the meeting, Jesús S. Mora, international coordinator of the AB10015 masitinib trial and an ALS neurologist, delivered a discussion titled, “Masitinib as an add-on therapy to riluzole is beneficial in the treatment of amyotrophic lateral sclerosis (ALS) with acceptable tolerability: Results from a randomized controlled phase 3 trial.”
“These final data confirm findings from the study’s interim analysis, showing that masitinib is effective in slowing down ALS disease progression,” Mora said, according to a news release. “This benefit is evident from the observed effect on a clinical assessment of daily functioning (Var. ALSFRS-R) and a significant improvement in terms of clinically relevant measures of quality-of-life and respiratory function.”
At the same meeting, Professor Luis Barbeito, head of the Neurodegeneration Laboratory at Institut Pasteur in Montevideo, Uruguay, presented, “Masitinib for the treatment of amyotrophic lateral sclerosis (ALS): Preclinical overview and future clinical development.”
“These Phase 3 clinical findings are strongly supported by equally compelling preclinical data, showing masitinib to generate a neuroprotective effect through targeting aberrant microglial cells and regulating neuroinflammation,” Barbeito said, according to the release.
“These data prove that masitinib is capable of slowing progression in ALS and effectively opens a new paradigm in the treatment of neurodegenerative diseases,” added Professor Olivier Hermine, president of AB Science’s Scientific Committee.
Masitinib is an orally administered therapy that targets mast cells and macrophages, which are important cells for immunity, by inhibiting a limited number of kinases. Because of its activity on mast cells and the subsequent inhibition of the inflammation process, masitinib can be effective against symptoms of inflammatory and CNS-associated diseases.
The European Medicines Agency (EMA) accepted a conditional marketing authorization application for masitinib to treat ALS, in October 2016. EMA’s decision to register masitinib for ALS is expected to be made public in coming months. The U.S. Food and Drug Administration granted masitinib orphan drug designation.