EAN 2020: Bruton kinase inhibitors show promise in MS

Multiple sclerosis

By Mardi Chapman

4 Jun 2020

Treatment of relapsing remitting MS with BTK inhibition appears to be well tolerated and effective on MRI, the European Association of Neurology (EAN) 2020 Virtual Congress was told.

Professor Daniel Reich, from the US National Institute of Neurological Disorders and Stroke, presented the results of a phase 2b study in about 200 patients randomised to either 12 weeks of the CNS-penetrating BTK Inhibitor SAR442168 or placebo.

The study tested 5mg, 15mg, 30mg and 60mg doses of the orally available small molecule.

Patients were mostly women (70%) with a median age of 37 years and 8-year duration of disease. Their EDSS was an average of 2.5, patients had experienced an average of 1.2 relapses in the previous year and they had 1.8 Gd-enhancing lesions at baseline.

Professor Reich said the study demonstrated a strong dose response relationship over 12 weeks in the primary outcome of the number of new Gd-enhancing lesions.

Compared with placebo, the 60 mg dose resulted in an 85% relative reduction in the number of new Gd-enhancing lesions.

Similarly in the secondary outcome, there was an 89% relative reduction in the number of new or enlarging T2 lesions compared to placebo.

“So we found a strong effect of the BTK inhibitor on the formation of MS lesions,” he said.

Other exploratory endpoints linked to CNS effects potentially on microglia are still under investigation, he said.

The study found about half of patients experienced adverse events but only 13% were considered to be treatment-related. Headache was the most common reported adverse event and transient ALT increases were also observed.

Only one serious adverse event – a hospitalisation for MS relapse – was reported.

“The findings indicate that SAR 442168 60 mg is well tolerated and effective at lowering MRI lesions in relapsing MS patients, supporting its continued development in phase 3,” he concluded.

In a late breaking session, Professor Xavier Montalban, director of the Multiple Sclerosis Centre of Catalonia in Spain, presented the open-label extension to a phase 2 study of the BTK inhibitor evobrutinib in relapsing MS.

The phase 2 study, published in the NEJM last year, found patients treated with 75 mg of daily evobrutinib had significantly fewer Gd-enhancing lesions during weeks 12 through 24 than controls.

The extension out to 108 weeks demonstrated that the magnitude of the benefit on relapse rate could be maintained long term.

It found the majority of treatment-related adverse effects such as nasopharyngitis or upper respiratory tract infections were usually mild or moderate.

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