Novartis Remibrutinib Hits Both Phase 3 REMODEL Endpoints in MS With No Liver Safety Signal

Novartis (NYSE: NVS) reported positive topline results from both REMODEL-1 and REMODEL-2, its identical Phase 3 trials of oral BTK inhibitor remibrutinib in relapsing multiple sclerosis (RMS). The drug beat teriflunomide on the primary endpoint of annualized relapse rate (ARR) and on every key secondary endpoint, and it did so with no liver safety signal (no cases meeting Hy’s Law criteria) across a development program that now spans more than 4,500 participants. NVS was up roughly 6.0% to about $161 intraday on September 1, from a $152.06 close on August 31 (Finnhub quote; Polygon prior close).

The readout is the first time a BTK inhibitor has delivered Phase 3 efficacy in MS without the hepatotoxicity that has defined the class. Sanofi’s tolebrutinib was rejected by the FDA late last year over drug-induced liver injury risk, and Merck’s evobrutinib was discontinued after liver toxicity. Roche’s fenebrutinib has posted Phase 3 wins in relapsing and primary progressive MS but is still shadowed by safety questions. Remibrutinib’s clean liver profile is the differentiator Novartis has been waiting for.

Both trials randomized roughly 2,000 patients 1:1 to remibrutinib 100 mg or teriflunomide. Beyond the ARR win, remibrutinib showed superiority on key secondary endpoints including MRI lesion counts, a positive trend in 3-month confirmed disability progression, and nominal significance on 6-month confirmed disability progression in a preplanned combined analysis of the two trials. Novartis did not disclose the exact ARR reduction in the topline release; full data come as a late-breaker at MSToronto2026.

Why It Matters

Remibrutinib is already de-risked. The FDA approved the 25 mg dose as Rhapsido for chronic spontaneous urticaria in September 2025, and the EMA followed in April 2026. That means the MS readout is a label expansion for an approved molecule rather than a bet on a wholly unproven drug. MS affects nearly 3 million people worldwide, a far larger market than CSU, and an oral with high efficacy plus a clean liver profile would slot in alongside Novartis’s injectable franchise.

The company plans to submit remibrutinib for RMS to health authorities globally. Novartis said the disability-progression signals and the safety record are what it will lean on to argue for a differentiated benefit-risk profile.

What to Watch Next

The MSToronto2026 late-breaker will show the actual ARR reduction and the disability-progression curves, which decide how strongly remibrutinib stacks up against fenebrutinib and existing oral options. Watch also for the open-label extension and the SPMS program (REMASTER), which would broaden the franchise beyond RMS. On the BTK inhibitor competitive set, see our Biogen BIIB091 coverage.

Novartis press release