Sanofi's experimental BTK inhibitor SAR442168 significantly cuts disease activity in relapsing MS: study

Sanofi announced Thursday that the highest dose of the experimental drug SAR442168 led to an 85% relative reduction of new Gd-enhancing T1 hyperintense lesions in a Phase IIb study of patients with relapsing forms of multiple sclerosis. The company reported in February that the BTK inhibitor hit the primary endpoint of the trial, with the oral, brain-penetrant, selective small molecule significantly reducing disease activity associated with MS as measured by magnetic resonance imaging (MRI).

"We believe that [SAR442168] shows promise for reducing both neuroinflammation and neurodegeneration," commented John Reed, Sanofi's global head of R&D. "As we go forward, we will explore whether our brain-penetrant BTK inhibitor offers strong efficacy and exceptional safety for a broad spectrum of MS patients with either relapsing or progressive forms of disease," Reed said, adding "our Phase III programme is moving rapidly to initiate four pivotal clinical trials."

The Phase IIb study was designed to assess the dose-response relationship after 12 weeks of treatment with SAR442168 at doses ranging from 5mg to 60mg, by measuring the number of new brain lesions on MRI. In one group, 64 patients with recurring MS received one of four doses of SAR442168 for the first 12 weeks, then crossed over to placebo for four weeks. Meanwhile, in the second group, 66 patients with recurring MS  received four weeks of placebo before crossing over to SAR442168.

According to Sanofi, in the primary objective measuring the number of new Gd-enhancing T1 hyperintense lesions, a multiple comparison procedure with modelling was applied to the dose-response data, revealing the exponential model provided the best fit. The company added that for the secondary goal measuring the number of new or enlarging T2 hyperintense lesions, the linear model was the best fit, and compared to placebo, treatment with SAR442168 60mg resulted in an 89% relative reduction.

Sanofi noted that no new safety signals were identified in the trial with one serious adverse event reported in a patient treated with SAR442168 over 12 weeks.

Commenting on the findings, principal investigator Daniel Reich said "in the context of compelling, emerging data about the role of the brain’s innate immune system in smoldering MS lesions, there is also good reason to believe that SAR442168 - due to its molecular mechanism of action and ability to cross the blood-brain barrier - may have additional effects that we need to study more deeply."

Sanofi obtained global rights to develop and commercialise the drug, previously known as PRN2246, under an agreement with Principia Biopharma potentially worth more than $800 million.

For related analysis, see Physician Views snap poll results: Neurologists positive on the potential promise of BTK inhibitors in MS, and KOL Views Results: BTK inhibitors like Sanofi's SAR442168 may have big role in progressive MS, says leading neurologist.

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