1st Relapsing MS Patient Enrolls in Phase 3 Trial of Oral SAR442168

A first person has enrolled in Sanofi’s Phase 3 trial evaluating SAR442168, an oral BTK inhibitor intended to treat relapsing forms of multiple sclerosis (MS), Sanofi’s partner, Principia Biopharma, announced.

“We are delighted that Sanofi has initiated … [this] trial in patients with relapsing MS,” Roy Hardiman, chief business officer at Principia, said in a press release.

SAR442168, formerly known as PRN2246, was discovered by Principia and is now being developed in collaboration with Sanofi, which also holds commercialization rights.

It is a small molecule inhibitor of the enzyme Bruton tyrosine kinase (BTK), which plays a key role in the activity and survival of immune B-cells. These cells are thought to drive inflammation in the central nervous system (CNS; the brain and spinal cord) of people with MS.

By blocking the BTK enzyme, SAR442168 is expected to lower inflammation both in the CNS, due to its ability to cross the blood-brain barrier, and throughout the body. Of note, the blood-brain barrier is a highly selective membrane that separates the brain from circulating blood and harmful molecules it might be carrying, like viruses or bacteria.

The Phase 3 trial, called GEMINI 1 (NCT04410978), will assess the safety and efficacy of SAR442168 against Aubagio (teriflunomide) in up to 900 adults, ages 18 to 55, with relapsing forms of MS.

Its main goal is the reduction in the number of MS relapses — measured by the annualized relapse rate (ARR) — in patients given SAR442168 daily compared with those given a daily 14 mg dose of Aubagio (an approved MS therapy by Sanofi) after about 36 months (three years).

Additional goals are the effects of treatment on disability progression, MRI lesions, cognitive performance, and quality of life among patients in these two groups.

GEMINI 1 is part of a larger Phase 3 clinical program launched by Sanofi to assess the therapeutic potential of SAR442168 in MS. Others are its twin study, GEMINI 2 (NCT04410991), and HERCULES (NCT04411641), assessing the safety and efficacy of SAR442168, against a  placebo, at delaying disability progression in up to 1,290 patients with non-relapsing (non-active) secondary progressive MS.

Eligible patients are being recruited for all three trials in the U.S. According to available information, GEMINI 1 and HERCULES are recruiting participants at a single site in Georgia, and GEMINI 2 at one site in Florida and in Louisiana.

Under the terms of a collaboration agreement between the two companies in 2017, Principia will be eligible to receive a $50 million milestone payment from Sanofi once dosing of patients in GEMINI 1 begins.