Novartis Reports Lower Relapse Rates and No Hy's Law Cases in Phase 3 Remibrutinib MS Trials

Novartis (NYSE:NVS) reported that its experimental multiple sclerosis treatment remibrutinib reduced annualised relapse rates by more than 30% compared with Sanofi’s Aubagio (teriflunomide) in two Phase 3 clinical trials, with no cases of Hy’s Law liver injury identified among patients receiving the investigational drug.

Shares in the Swiss pharmaceutical company declined on Monday following the release of the results on Friday.

The REMODEL-1 and REMODEL-2 trials evaluated remibrutinib in patients with relapsing multiple sclerosis, comparing its efficacy and safety with teriflunomide, an established treatment for the condition.

Novartis said the studies met their primary endpoints, demonstrating reductions in annualised relapse rates of 35.2% and 31.2%, respectively.

Remibrutinib Reduces Annualised Relapse Rates in Both Studies

In REMODEL-1, the annualised relapse rate was 0.073 among patients receiving remibrutinib, compared with 0.112 for those treated with teriflunomide.

This represented a relative reduction of 35.2%.

In REMODEL-2, the annualised relapse rate was 0.080 for remibrutinib and 0.116 for teriflunomide, corresponding to a reduction of 31.2%.

Annualised relapse rate was the primary endpoint in both studies and measures the average number of disease relapses per patient over a year.

The trials enrolled approximately 2,000 patients in total, who received either remibrutinib at a dose of 100 mg or teriflunomide.

The findings provide comparative efficacy data for remibrutinib in relapsing multiple sclerosis, a condition characterised by episodes of neurological symptoms associated with inflammatory activity in the central nervous system.

Disability Progression and MRI Findings

Novartis also reported results from secondary measures assessing disability progression and disease activity detected through magnetic resonance imaging.

More than 92% of patients receiving remibrutinib remained free from disability progression confirmed at six months during the 24-month observation period.

The company reported a 29.2% relative reduction in the risk of six-month confirmed disability progression compared with teriflunomide.

This finding achieved nominal statistical significance, which does not necessarily establish significance after adjustment for multiple comparisons.

MRI assessments also indicated reductions in inflammatory lesion activity.

In REMODEL-1 and REMODEL-2, remibrutinib reduced T2 lesion activity by 65% and 70%, respectively, compared with teriflunomide.

Gadolinium-enhancing T1 lesions, another measure of inflammatory disease activity, were reduced by 66% across the two trials.

A pooled analysis found that 55% of patients receiving remibrutinib had no relapses, confirmed disability progression or MRI disease activity, compared with 32.1% of those receiving teriflunomide.

These findings provide additional information about the treatment’s effects on clinical and imaging measures of multiple sclerosis activity.

Liver Safety Findings Show No Hy’s Law Cases

Liver safety was a particular area of interest in the trials because other investigational drugs in the same class have been associated with liver-related adverse events.

Novartis reported no cases meeting Hy’s Law criteria among patients treated with remibrutinib.

Hy’s Law is used in clinical drug development to identify patterns of laboratory abnormalities that may indicate a risk of serious drug-induced liver injury.

Elevations in liver enzymes exceeding three times the upper limit of normal were recorded in 2% of patients receiving remibrutinib, compared with 7.4% of those receiving teriflunomide.

The absence of Hy’s Law cases in these studies is a trial safety finding and does not establish that the treatment carries no risk of liver injury.

Further safety evaluation will form part of the regulatory review process.

Adverse Events and Treatment Discontinuations

Pooled safety data from REMODEL-1 and REMODEL-2 showed that 79.5% of patients receiving remibrutinib experienced adverse events of any severity, compared with 81.5% of patients treated with teriflunomide.

Serious adverse events were reported in 6% of the remibrutinib group and 7% of the teriflunomide group.

Treatment discontinuations attributed to adverse events occurred in 3.1% of patients receiving remibrutinib, compared with 5.8% of those receiving teriflunomide.

Two deaths were recorded among patients treated with remibrutinib during the trials.

One resulted from accidental carbon monoxide poisoning, while the other was attributed to suicide.

Study investigators assessed both deaths as unrelated to treatment.

The pooled findings provide comparative information about adverse events and treatment discontinuation rates across the two study populations.

Novartis Plans Global Regulatory Submissions for Multiple Sclerosis

Following the Phase 3 results, Novartis intends to seek regulatory approval for remibrutinib as a treatment for relapsing multiple sclerosis in markets worldwide.

The company has not specified a submission timetable in the supplied announcement.

Remibrutinib is already marketed under the brand name Rhapsido for other indications, although at a different dose.

The 25 mg formulation received approval in the United States for chronic spontaneous urticaria in September 2025, followed by European approval for the same condition in April 2026.

In October 2026, the US Food and Drug Administration also approved Rhapsido for symptomatic dermographism.

The multiple sclerosis programme uses a 100 mg dose and represents a separate indication requiring its own regulatory assessment.

The REMODEL trial results will support Novartis’s planned applications, with regulators expected to evaluate the efficacy and safety evidence before determining whether to authorise the treatment for relapsing multiple sclerosis.

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