Masitinib Slows Disability Progression in PPMS and Non-active… – Multiple Sclerosis News Today

AB Sciencesmasitinib significantly slowed disability progression in people with primary progressive multiple sclerosis (PPMS) and non-active secondary progressive MS (SPMS) at a lower dose of 4.5 mg/kg a day, top-line results from a Phase 2b/3 clinical trial show.

Masitinib, formerly known as AB1010, is an oral therapy that inhibits the activity of cells in the innate immune system, specifically mast cells, microglia, and macrophages. In doing so, the therapy is expected to limit the inflammatory processes that cause damage to the nervous system in MS.

It may also have applications in other conditions, including other neurological diseases and certain cancers.

People with primary progressive (PPMS) and non-active secondary progressive (nSPMS) forms of multiple sclerosis account for half of all MS patients, Patrick Vermersch, PhD, a professor at University of Lillein France and a trial investigator, said in an AB Science press release.

PPMS is estimated to affect about 15% of all MS patients, while non-active SPMS affects about 30% to 35%.

While numerous treatments based on targeting of B-cells and T-cells of the adaptive immune system are available for patients with relapsing forms of MS, these strategies have failed or had inconclusive results in PPMS and nSPMS. Consequently, there remains a very high medical need for people with progressive MS forms, Vermersch added.

In the AB07002 Phase 2b/3 clinical trial (NCT01433497), a group consisting of 301 MS patients were enrolled, with 200 randomized to 4.5 mg/kg of masitinib daily, and 101 to a placebo. The trials primary endpoint (goal) was changes in disability, measured through the Expanded Disability Status Scale (EDSS) score, from the studys start (baseline) through week 12 to week 96 of treatment.

Results showed the primary endpoint was met, with significantly lower increases in EDSS seen in the masitinib-treated group compared to the placebo group. This treatment effect was maintained for both the PPMS and non-active SPMS subpopulations. (Higher EDSS score represent worsening disability levels.)

Treatment also significantly delayed disease progression, as measured by the time to reach an EDSS score of 7.0 functionally, this score means a person requires the use of a wheelchair.

[T]he results from this study represent a scientific breakthrough because this is the first time that the novel strategy of targeting the innate immune system via mast cells and microglia has been able to significantly slow progression of clinical disability in progressive forms of MS, Vermersch said. These data are extremely encouraging, and may provide new hope for progressive MS patients.

Added Olivier Hermine, MD, PhD, president of AB Sciences scientific committee:This positive result in progressive MS is an important new finding that further validates the mechanism of action of masitinib in neurodegenerative diseases.

Masitinibs safety was consistent with the therapys known profile. Overall, 95% of people on 4.5 mg/kg masitinib daily, and 87.1% of those in the corresponding placebo group, experienced at least one reported adverse event. AB Science did not specify what these events were.

People in another trial arm were given masitinib a daily dose of 6.0 mg/kg, with titration starting at 4.5 mg/kg/day. This group consisted of 310 people, with 203 treated with masitinib and 107 given a placebo. No significant beneficial effects over placebo with masitinib at this higher dose were seen.

Further details were not released, which AB Science said would be given at an upcoming scientific conference. The company also announced a new patent filing for masitinib based on AB07002 trial results, and said it will be in contact with regulatory authorities to discuss further development of masitinib as a treatment for progressive forms of MS.

Masitinib is also being tested patients withamyotrophic lateral sclerosis (ALS), where a single-site Phase 3 trial (NCT03127267) is expected to open in March in Montreal, Canada. A Phase 3 trial (NCT01872598) in people withAlzheimers diseaseor probable Alzheimers also recently concluded.

This MS trial is the second piece of supportive evidence delivered by the masitinib clinical program. The first one was thepositive Phase 2B/3 study with masitinib in amyotrophic lateral sclerosis, Hermine said.

The two studies taken together clearly demonstrate that targeting the innate immune system via macrophage/microglia and mast cells, as masitinib does, is one of the right strategies to treat neurodegenerative disorders, Hermine concluded.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.

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Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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Masitinib Slows Disability Progression in PPMS and Non-active... - Multiple Sclerosis News Today