Sanofi to Detail Trial Results of Oral Relapsing MS Therapy Online on Thursday

Sanofi will host an online science session to present results of a Phase 2b clinical trial testing the safety and efficacy of its investigational, oral BTK inhibitor SAR442168 in people with multiple sclerosis (MS).

The virtual session, owing to the cancellation of the American Academy of Neurology (AAN)’s 2020 annual meeting due to the COVID-19 pandemic, is set for Thursday, April 23, from 8:00-9:00 am EST. Registration can be found here.

SAR442168 is designed to block the activity of a protein called Bruton’s tyrosine kinase (BTK). This protein is important for the inflammation-driving activity of certain types of immune cells, most notably B-cells. By blocking BTK, SAR442168 is expected to lessen the inflammation that causes nervous system damage in MS.

The investigational therapeutic is being developed by Sanofi, in collaboration with Principia Biopharma.

“During these unprecedented times we remain committed to sharing results that allow us to advance the understanding of multiple sclerosis and the impact our potential brain-penetrant BTK inhibitor could have on the lives of people living with this disease,” John C. Reed, MD, PhD, the global head of research and development at Sanofi, said in a press release.

“Our virtual session will provide the opportunity for an important scientific exchange and a forum for sharing the recent clinical results obtained with our brain-penetrant BTK inhibitor for multiple sclerosis,” Reed added.

Results of a Phase 1 trial (ACTRN12617001457336) conducted in healthy volunteers showed SAR442168 (previously known as PRN2246) to have a good safety profile, with no serious treatment-related adverse events reported.

Findings also showed that the therapy was present in the fluid around the brain and spinal cord in dosed individuals. This is important, as it shows that SAR442168 can cross the blood-brain barrier — a barrier that prevents harmful substances in the blood from entering the brain. Getting past this barrier and into the brain is critical for therapies designed to affect the nervous system.

SAR442168 was then evaluated in a Phase 2b clinical trial (NCT03889639), which enrolled 120 people with relapsing forms of MS, which include relapsing-remitting MS and active secondary progressive MS.

Participants were randomized into two groups of 60 each. In one group, they were given placebo for four weeks, then assigned to one of four doses of SAR442168 (5, 15, 30, or 60 mg), as a daily tablet for 12 weeks, for a total study period of 16 weeks. The second group went through the same treatment regime, but in the opposite order — first, an assigned SAR442168 dose for 12 weeks, then four weeks of placebo.

This type of trial, where all receive both the study therapy and a placebo, is called a crossover study. The advantage of this type of trial is that each participant can provide their own placebo data. As such, there is no a need for a study arm where patients only receive an inactive placebo.

“By applying modern trial design elements, we developed a compact, MRI-based trial for proof-of-concept and dose-finding for SAR442168 in patients with relapsing MS without the need for a placebo-only arm,” the researchers wrote in one of the abstracts accepted for presentation at AAN 2020.

This abstract is titled “Design of a Phase 2b Dose-finding Trial to Evaluate Safety and Efficacy of the CNS-penetrant BTK Inhibitor SAR442168 in Patients with Relapsing Forms of Multiple Sclerosis.”

Previous results from the Phase 2B trial showed that SAR442168 met the study’s primary goal — a significant reduction in the number of new lesions visible on brain MRI scans.

Another SAR442168-related abstract also accepted for presentation at AAN — called “Central Effects of BTK Inhibition in Neuroinflammation” — shows that, in addition to its effect on B-cells, SAR442168 also inhibits the activity of microglia, a type of cell present in the brain and spinal cord that act as the main form of immune defense in the central nervous system.

“BTK-dependent inflammatory signaling in microglia can be modulated using brain-penetrant BTK inhibitors, which could abrogate microglia-driven neuroinflammation implicated in disease progression in MS,” researchers wrote in the abstract.

At the upcoming Sanofi virtual scientific session, more detailed data regarding the efficacy and safety outcomes of the trial will be presented. The mechanism of action of SAR442168 (how it is thought to work) and the trial’s design will also be discussed.