Roche has shared long-term phase 2 data on its BTK inhibitor fenebrutinib in relapsing multiple sclerosis (MS), providing evidence of durability over 96 weeks to build out its case ahead of the release of pivotal trial results.
BTK inhibitors have struggled in relapsing MS, with Merck KGaA axing its candidate after chalking up failures in two phase 3 trials in the setting. Meanwhile, Sanofi's tolebrutinib failed both of its phase 3 relapsing MS trials, although the blow was softened somewhat by a win in another form of the disease. As rivals have fallen away, Roche has continued to work toward readouts from two phase 3 trials in relapsing MS.
The first data from Roche’s phase 3 program, which also includes a study in primary progressive MS, are due at the end of the year. Ahead of the readouts, Roche provided a fresh cut of data from the phase 2 trial that supported its decision to run pivotal studies in relapsing MS.
Patients who took fenebrutinib for up to 96 weeks had an annualized relapse rate of 0.06. Roche saw no disability progression, as measured by the Expanded Disability Status Scale (EDSS), in the open-label extension. No active brain lesions were detected.
For comparison, Sanofi reported (PDF) an annualized relapse rate of 0.17 at Week 72 of its phase 2 tolebrutinib trial in relapsing MS, with a rate of 0.20 at Week 120. Sanofi said mean EDSS remained stable to Week 120.
Roche said that one patient on fenebrutinib had an asymptomatic increase in a liver enzyme after 16 weeks on the BTK inhibitor, with the case resolving after the patient stopped treatment. The FDA put a partial hold on Roche’s phase 3 relapsing MS trials in 2023 over two cases of elevated enzymes and bilirubin that suggested drug-induced liver injuries. Similar adverse events have been seen on other BTK inhibitors.
Despite the adverse events, Roche has continued to make the case that fenebrutinib has advantages over other BTK inhibitors. The molecule is noncovalent and, Roche claims, more potent and selective. Teresa Graham, CEO of Roche’s pharma business, used the company’s first-quarter earnings call in April to outline why fenebrutinib could succeed where rival molecules have struggled.
“We do believe that we just, frankly, have a better BTK and one that we were able to bring forward into phase 3s at what we believe to be the most appropriate dose,” Graham said. “I think that's the other thing that has potentially impacted some other trials, is they just weren't able to get to the level of dosing that they needed. We believe we've gotten to the level of dose that we need.”