Roche’s fenebrutinib posted eight deaths against Aubagio’s one across its two phase 3 relapsing MS trials, and at the American Academy of Neurology Annual Meeting Wednesday, the company spelled out the causes.
The deaths scattered across causes and timing: neurocryptococcosis gattii, pneumonia, Type 1 diabetes complications, bleeding, suicide, injuries from an accident, and one unknown cause. A third trial in primary progressive MS showed a similar split: seven deaths on fenebrutinib versus one on Ocrevus, with investigators ruling all PPMS fatalities unrelated to the study drug.
The fatality imbalance piles onto existing BTK class concerns. Fenebrutinib has been linked to liver toxicity, as have other BTK inhibitors; in the RMS trials, liver enzyme elevations were comparable to Aubagio’s, and one patient on each arm met Hy’s Law criteria.
Roche used AAN to release secondary endpoints that could help its filing. Active inflammation markers fell 70.7% and 77.6%; chronic disease burden dropped 76% and 82.5%. On disability progression, fenebrutinib posted a 20% and 13% lower risk versus Aubagio, but the disability endpoint didn’t reach statistical significance.
Roche plans to submit data from both its RMS and PPMS programs to regulators; consensus puts fenebrutinib revenues at 1.1 billion Swiss francs ($1.4 billion) by 2030. Novartis won’t be far behind, still moving toward pivotal data on a competing BTK inhibitor that has shown a potentially differentiated safety profile.
Sarah Chen