AB Science OK’d to Start Masitinib Phase 3 Trial for Progressive MS
The French Health Authority has approved AB Science’s request to launch a Phase 3 clinical trial to confirm the safety and effectiveness of its lead candidate masitinib in adults with primary progressive multiple sclerosis (PPMS) and nonactive secondary progressive MS (SPMS).
“We are very excited to initiate this confirmatory phase III study with masitinib in progressive forms of multiple sclerosis,” Patrick Vermersch, MD, PhD, the trial’s principal investigator, said in a press release. He is a professor of neurology at the University of Lille, France.
While progressive forms of the disease “currently account for approximately 50% of MS cases,” Vermersch said, “the vast majority of treatments … apply mainly to the relapsing remitting forms of the disease.”
Masitinib is an oral medication that works by blocking tyrosine kinase, an enzyme essential for the activity of innate immune cells — such as mast cells, microglia, and macrophages — which are thought to drive neuroinflammation and neurodegeneration in progressive MS.
The innate immune system is the body’s first line of defense and is made of cells people are born with, while the adaptive immune system, which is thought to be the main contributor to relapsing forms of MS, is acquired through exposure to a given microbe or molecule.
By suppressing innate immune cells, the therapy is expected to slow disease progression in progressive forms of MS.
Olivier Hermine, MD, PhD, AB Science’s co-founder and president of the scientific committee, said, “To date, there is no treatment capable of effectively targeting those cells of the innate immune system that are associated with the [development] of progressive forms of multiple sclerosis. Masitinib selectively targets these cells.
“Furthermore, masitinib is not an immunosuppressive treatment, which is particularly important in MS patients who need to receive long-term treatment and who, in certain cases, already have a weakened immune system due to previous treatments or because of their age,” added Hermine, who is also a member of the French Academy of Sciences.
Results from a previous Phase 2b/3 trial, called AB07002 (NCT01433497), showed that two years of treatment with masitinib, at a daily dose of 4.5 milligrams per kilogram (mg/kg), was superior to a placebo at slowing disability progression in adults with PPMS and nonactive SPMS — meeting the trial’s main goal.
Changes in patients’ disability were assessed with the expanded disability status scale (EDSS).
Involving 656 patients, the European study also showed that this treatment dose significantly reduced the risk of first disability progression by 42% and the risk of confirmed (three-month) disability progression by 37%, relative to a placebo.
Patients who received masitinib also had a 98% lower risk of reaching an EDSS score of 7.0 — reflecting a level of disability severe enough that the patient is restricted to a wheelchair — compared with those in the placebo group.
These positive findings supported AB Science’s plans to launch a Phase 3 trial to confirm the benefits of this treatment dose in a larger patient population.
The upcoming international Phase 3 trial, called AB20009 (2021-000639-30), will evaluate masitinib’s safety and effectiveness against a placebo in up to 800 adults, 18–65 years, with PPMS and nonactive SPMS.
The study is expected to recruit patients at 75 sites in Europe, the U.S., Canada, Israel, and South Africa.
Eligible patients must have an EDSS score between 3.0 and 6.0, covering those with moderate disability but maintaining their ability to walk unaided through those already requiring a walking aid. They must also have no T1 gadolinium-enhancing brain lesions on MRI scans — a marker of MS lesions with active inflammation.
Participants will be randomly assigned to receive either masitinib — starting at a daily dose of 3.0 mg/kg and increased to 4.5 mg/kg after four weeks — or a placebo for up to two years.
The trial’s main goal is to assess whether masitinib is superior to a placebo at delaying confirmed (three-month) disability progression, defined as a 1-point worsening when EDSS score at study start is 5.5 or lower, or a 0.5-point worsening if the score is higher than 5.5.
Secondary goals include time to confirmed EDSS progression lasting at least six months, changes in EDSS scores over two years, and time to EDSS score of 7.0.
Changes in validated measures of motor and cognitive function will also be assessed, as well as changes in brain volume and lesions, relapses, quality of life, fatigue, and depression. An additional goal is to measure changes in the levels of nerve damage biomarkers in a subgroup of 200 patients of preselected trial sites.