The Food and Drug Administration has accepted Roche's application for its experimental multiple sclerosis pill fenebrutinib, granting a priority review that could lead to approval in both relapsing and primary progressive forms of the disease. If cleared, it would be the first BTK inhibitor approved in both settings. Roche's submission rests on three late-stage studies that met their primary goals, but the path to a decision is complicated by safety signals that have dogged the drug class.
Fenebrutinib belongs to a family of BTK inhibitors originally developed for cancer, now being repurposed for autoimmune conditions. In MS, however, the class has struggled: candidates from Merck KGaA and Sanofi were slowed by liver-related side effects and missed their goals in large relapsing-MS trials, and Sanofi's medicine was rejected in the U.S. partly over safety concerns. Roche's drug, by contrast, succeeded in its pivotal trials, but its development was previously paused by a partial clinical hold.
Safety remains the main open question. In one study, a patient had liver enzyme elevations meeting Hy's law, a threshold linked to higher risk of death or liver failure. Across two of the three Phase 3 trials, eight deaths occurred among fenebrutinib recipients versus one in a comparator group. Roche said the deaths happened at different times with various causes, and described the drug's overall safety profile as manageable based on data from more than 2,700 participants. The FDA's review will weigh these concerns against the drug's demonstrated efficacy. [Source: BioPharma Dive]