Sanofi Hits the Mark in Phase II MS Trial with Experimental BTK Inhibitor

Multiple Sclerosis_2

Sanofis investigational Bruton's tyrosine kinase inhibitor SAR442168 hit the mark in a mid-stage multiple sclerosis trial. The company said the treatment significantly reduced disease activity as measured by magnetic resonance imaging.

France-based Sanofi is assessing the drug as a potential treatment for patients with relapsing forms of the disease. In the Phase II study, Sanofi looked at dose levels ranging from 5 mg to 60 mg. The study showed that the 60 mg dose provided an 85% relative reduction of new Gd-enhancing T1 hyperintense lesions and an 89% relative reduction in T2 hyperintense lesions, which was a secondary endpoint.

No new safety signals were observed in the trial but, there was a single serious adverse event of MS relapse reported.

The cause of multiple sclerosis (MS) is not known and there is no cure for the debilitating disease. It is estimated that about 2.3 million people globally live with the disease, with hundreds of thousands more who remain undiagnosed. Despite current treatments, many MS patients continue to accumulate disability, and one in four MS patients suffers from progressive forms of the disease with limited or no treatments available.

SAR442168, which Sanofi obtained in a $765 million deal with Bay Area-based Principia Biopharma, is an oral, brain-penetrant, selective small-molecule inhibitor of BTK. The drug is designed to access the brain and spinal cord by crossing the blood-brain barrier and impact immune cell and brain cell signaling. The BTK inhibitor modulates both adaptive (B-cell activation) and innate (CNS microglial cells) immune cells thought to be linked to neuroinflammation and neurodegeneration in the brain and spinal cord, the clinical significance of which is under investigation.

John Reed, Sanofi’s Global Head of Research and Development, said the company believes SAR442168 shows promise in reducing both neuroinflammation and neurodegeneration, markers of disability progression in multiple sclerosis patients.

The effect on brain lesions seen in our Phase IIb study is encouraging. 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 the disease,” he said in a statement.

Now, the company plans to push SAR442168 into late-stage studies. Specifically, Reed said the Sanofi is moving rapidly to initiate four pivotal Phase III clinical trials. 

Principal study investigator Daniel Reich, a senior investigator at the National Institutes of Health and chief of the Translational Neuroradiology Section in the National Institute of Neurological Disorders and Stroke, said the Phase IIb study provides hope that SAR442168 may become an important treatment for relapsing MS.

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. In my view, it’s important to move forward with broad and innovative testing of this BTK inhibitor in Phase III studies in MS,” Reich said in a statement.

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