Roche's oral MS hope fenebrutinib hits the mark in phase 3
Levi Garraway, Roche's chief medical officer and head of global product development.
Roche has built the evidence for its oral BTK inhibitor fenebrutinib in multiple sclerosis (MS) with two phase 3 readouts that keep it on track for regulatory filings next year.
The brain-penetrating drug has hit the mark in patients with relapsing MS in the FENhance 2 study and primary progressive MS in FENtrepid, and now Roche is only waiting for the results of FENhance 1 in relapsing MS – due in the first half of next year – before filing for approval.
That timeline puts Roche hot on the heels of Sanofi, whose rival brain-penetrant BTK inhibitor tolebrutinib was submitted for approval earlier this year as a treatment for non-relapsing secondary progressive MS, with a decision due by 28th December – which has been delayed by three months after a request by the FDA for additional data.
Sanofi's decision to file for nrSPMS only comes after tolebrutinib failed to achieve its primary objective in two other phase 3 trials that involved patients with relapsing forms of MS. Meanwhile, another BTK inhibitor being developed for MS, Merck KGaA's evobrutinib – also failed late-stage testing and has been abandoned.
That puts Roche in a strong position with fenebrutinib, which seems to be slightly ahead of other candidates for MS in the class, including Novartis' remibrutinib and InnoCare Pharma's orelabrutinib. There are limited options for MS, particularly progressive forms, and analysts have predicted multibillion-dollar sales for the oral BTK class if it reaches the market, with Leerink suggesting fenebrutinib could make $1 billion-plus on its own.
In FENhance 2, fenebrutinib met its primary endpoint, showing significantly reduced relapses compared to Sanofi's older oral MS drug Aubagio (teriflunomide), which is also available as a generic.
In FENtrepid, fenebrutinib was able to slow disability progression as effectively as treatment with Roche's Ocrevus (ocrelizumab), given intravenously or by injection, which is currently the only FDA-approved therapy for primary progressive MS and generated sales of more than $5.7 billion last year.
Roche also said that liver side effects were consistent with previous trials of fenebrutinib, which is an encouraging finding given that the drug was previously under an FDA partial clinical hold in November 2023 while cases of elevated liver enzymes and bilirubin in the FENhance 1 trial were investigated.
"These unprecedented results suggest that fenebrutinib could potentially become a best-in-disease medicine," said Levi Garraway, Roche's chief medical officer, who added that the data "offer new hope for people living with MS, and they reaffirm our enduring commitment to the MS community."
