Novartis’ MS drug succeeds in phase 3 trials; “No liver toxicity signals”

Novartis achieved its goals in two phase 3 clinical trials of Rapsido, a treatment for relapsing multiple sclerosis (MS), without liver toxicity signals.

Novartis said on the 1st (local time) that remibrutinib, the active ingredient in Rapsido, met the primary endpoint of reducing annualized relapse rates in the phase 3 REMODEL-1 and -2 trials in patients with relapsing MS. Fierce Pharma reported the news that day.

Compared with Sanofi’s existing treatment Aubagio (active ingredient: teriflunomide), Rapsido reduced annualized relapse rates to a greater extent. It also improved inflammatory brain lesions and showed clinically meaningful reductions in secondary endpoints related to disability progression.

Novartis particularly emphasized that “there were no liver toxicity signals in either trial, and there were no cases meeting Hy’s Law criteria.” Hy’s Law is a criterion used to identify patients at high risk of severe drug-induced liver injury. About 2,000 people participated in the two trials and received Rapsido or Aubagio in a 1-to-1 ratio.

The BTK inhibitor class has fallen short of expectations in MS, with repeated liver toxicity signals. The U.S. Food and Drug Administration (FDA) has previously placed clinical holds on competing drugs from Sanofi and Roche.

Sanofi’s tolebrutinib was denied FDA approval for nonrelapsing secondary progressive MS. In a complete response letter, the FDA cited the risk of severe drug-induced liver injury, including six cases that met Hy’s Law criteria.

Roche’s fenebrutinib received a partial clinical hold in 2023 after two cases of elevated liver enzyme levels. Roche recently reported one case meeting Hy’s Law criteria associated with its BTK drug in the phase 3 FENhance 1 study in relapsing MS.

A Novartis spokesperson confirmed to Fierce Pharma that there were no deaths related to Rapsido in the REMODEL trials.

Shreeram Aradhye, Novartis’ chief medical officer (CMO), said, “Despite advances in treatment, there remains an unmet need for oral therapies that provide robust relapse prevention and delay disability progression while maintaining a favorable safety profile.”

Rapsido received its first FDA approval in September 2025 as a treatment for chronic spontaneous urticaria (CSU). Novartis plans to introduce a new oral option in MS and administer it earlier than biologics.

Before this announcement, Novartis halted development of the CD19 candidate across several clinical trials after it emerged that three patients had died from severe immune-related complications in trials of the autoimmune CAR T-cell candidate rapcabtagene autoleucel. This included a phase 1/2 trial in patients with relapsing MS.