The first patient has been dosed in a Phase 2B clinical trial evaluating the safety, efficacy, and tolerability of SAR442168 in people with relapsing multiple sclerosis (MS). SAR442168, formerly known as PRN2246, is being developed by Principia Biopharma, in collaboration with Sanofi Genzyme, for MS and other central nervous system (CNS) disorders.
The Phase 2B trial (NCT03889639) also is a dose-finding study to determine what SAR442168 dose is most effective without causing serious adverse events.
“We are delighted that the first patient has been dosed in Sanofi’s Phase 2b dose-finding trial in patients with relapsing multiple sclerosis,” Martin Babler, president and CEO of Principia, said in a press release.
SAR442168 is designed to cross the blood-brain barrier, and block Bruton’s tyrosine kinase (BTK) — an important signaling molecule that triggers the proliferation of immune B-cells in the brain, and promotes neuroinflammation. The BTK-mediated increase in the number of B-cells, and the associated brain inflammation, is linked to the damage found in MS and other CNS disorders.
SAR442168 treatment thus has the potential to specifically regulate cells that drive CNS autoimmunity and inflammation processes.
Results from an Australian Phase 1 study (ACTRN12617001457336) in healthy volunteers showed that SAR442168 was well-tolerated by the participants. Importantly, the therapy was found in the cerebrospinal fluid (present in the brain and spinal cord), indicating that this experimental therapeutic can successfully cross the blood-brain barrier — a shield that protects the brain from toxins and pathogens that may be present in the blood.
The ability to cross the blood-brain barrier is vital for any therapeutic that aims to have an impact on brain cells.
The trial also found that SAR442168 successfully bound to BTK in peripheral blood cells from the participants at clinically relevant doses.
“One challenge in developing medicines for CNS disorders has been achieving sufficient blood-brain barrier penetration. We are very enthusiastic about the potential of our CNS-penetrating BTK inhibitor, especially because in a Phase 1 clinical trial, we demonstrated exposure of SAR442168 in the CNS as well as BTK occupancy in peripheral blood,” Babler said.
Now, in the ongoing Phase 2B trial, the companies plan to enroll about 120 relapsing MS patients, ages 18 to 55. In this 24-week study, several doses of SAR442168 will be assessed to determine the correct dosage based on magnetic resonance imaging (MRI) assessments.
The trial is a crossover study, which means that the treatment plan is designed so that all patients receive both the treatment and the placebo, and will serve as their own control group. The enrollment is ongoing, and more information can be found on this link.
As per the collaboration between the two companies, Sanofi has the exclusive worldwide license to develop and commercialize SAR442168. The dosing of the first patient in the Phase 2B trial marks a key milestone in this licensing agreement, triggering a $30 million payment by Sanofi to Principia. Principia retained the option to co-fund the treatment’s Phase 3 development in exchange for other royalties in the U.S.