Sweden, Like France, OKs Start of Masitinib Trial in Progressive MS

The Swedish Medical Products Agency has approved AB Science’s request to launch in the country a confirmatory Phase 3 clinical trial of its lead candidate masitinib in adults with primary progressive multiple sclerosis (PPMS) and nonactive secondary progressive MS (SPMS).

The decision comes on the heels of a similar authorization by the French Health Authority. AB Science expects the upcoming trial to involve 75 sites in Europe, the U.S., Canada, Israel, and South Africa.

“This latest approval … represents a key step not only for the clinical program of masitinib in progressive forms of multiple sclerosis, but also for the overall masitinib pipeline in neurology,” Olivier Hermine, MD, PhD, AB Science’s co-founder and president of the scientific committee, said in a press release.

“To date, masitinib has demonstrated positive Phase 2B/3 results in three neurodegenerative disorders, namely, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and progressive forms of multiple sclerosis,” Hermine said.

The therapy’s success in these three conditions “clearly demonstrates that masitinib’s innovative targeting of the innate immune system is a valid strategy,” he said.

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“We are committed to continue masitinib’s clinical development program in each of these highly challenging neurological disorders, with an ultimate objective to improve patients’ lives,” Hermine added.

Masitinib, formerly known as AB1010, is an oral therapy designed to suppress the activity of innate immune cells — such as mast cells, microglia, and macrophages — which are thought to drive neuroinflammation and neurodegeneration in progressive MS. It works by blocking tyrosine kinase, a key enzyme for these cells’ activity.

The innate immune system 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.

Data from the previous AB07002 Phase 2b/3 trial (NCT01433497), which involved 656 adults with PPMS and nonactive SPMS, supported the benefits of masitinib, at a daily dose of 4.5 milligrams per kilogram (mg/kg), over a placebo.

Specifically, patients treated for two years with this dose showed significantly slower disability progression — as assessed with the expanded disability status scale (EDSS) — than those in the placebo group, irrespective of their type of progressive MS.

Masitinib also was associated with a 42% lower risk of first disability progression, a 37% reduced risk of disability progression lasting at least three months, and a 98% lower risk of a patient becoming restricted to a wheelchair, compared with a placebo.

The therapy’s safety profile was consistent with that reported in prior studies, with the most common treatment-related adverse events including diarrhea, nausea, rash, and changes in various blood assessments.

These positive findings prompted AB Science’s plans to launch a Phase 3 trial to confirm the benefits of this masitinib dose in a larger patient population.

Called AB20009 (2021-000639-30), the upcoming international trial will test the therapy against a placebo in up to 800 adults, 18–65 years, with PPMS and nonactive SPMS. Participants will be randomly assigned to receive either masitinib — starting at a daily dose of 3.0 mg/kg and increasing to 4.5 mg/kg after four weeks — or a placebo for up to two years.

The study’s main goal is to assess whether masitinib extends the time to disability progression lasting at least three months. Secondary goals include time to six-month confirmed disability progression, changes in EDSS scores over two years, and time to becoming wheelchair-bound.

Other goals include changes in motor and cognitive function, brain volume and lesions, disease relapses, fatigue, depression, and quality of life. In a subgroup of 200 patients of preselected trial sites, researchers also will measure changes in the levels of nerve damage biomarkers.