Novartis Remibrutinib Cuts MS Relapses in Phase III, Eyes $4B Opportunity

Key Points

• Remibrutinib met its Phase III relapse endpoint in both REMODEL studies, reducing annualized relapse rates by 35% and 31.2% versus teriflunomide. It also substantially lowered MRI lesion activity and improved measures of disease control.
• Novartis reported a broadly comparable safety profile, with fewer liver enzyme elevations and no Hy’s Law cases, though bleeding events remain a consideration for the BTK inhibitor class. U.S. regulatory filing is expected by year-end, supported by a priority review voucher.
• Novartis estimates remibrutinib could become a more than $4 billion MS product, targeting newly diagnosed patients and those switching from oral or anti-CD20 therapies. Further studies are evaluating switches from ocrelizumab and use in non-relapsing secondary progressive MS.

Novartis NYSE: NVS presented Phase III results for remibrutinib in relapsing multiple sclerosis, reporting that the oral Bruton’s tyrosine kinase inhibitor reduced relapse rates and MRI lesion activity versus teriflunomide in the REMODEL-1 and REMODEL-2 studies.

The company said global regulatory filings are underway, with a U.S. submission expected by the end of the year using a priority review voucher. Novartis is positioning remibrutinib as an oral treatment option that may provide disease control without chronic B-cell depletion.

REMODEL studies met relapse endpoint

Heinz Wiendl, professor and director of the Department of Neurology and Neurophysiology at the University of Freiburg and a member of the REMODEL steering committee, said the two double-blind, double-dummy trials compared remibrutinib 100 mg twice daily with teriflunomide in patients with relapsing MS who had evidence of active disease.

Remibrutinib reduced annualized relapse rates by 35% in REMODEL-1 and 31.2% in REMODEL-2, Wiendl said. He characterized the results as equating to approximately one relapse every 13 years among treated patients.

MRI measures also favored remibrutinib. The drug reduced annualized new or enlarging T2 lesions by 65.3% in one study and 70.3% in the other, while gadolinium-enhancing lesions were reduced by 66% in both trials, according to Wiendl.

On disability measures, the pooled analysis showed a statistically significant reduction in six-month confirmed disability progression. Wiendl said the reduction was approximately 30% for progression independent of relapse activity, or PIRA, using a strict definition. The three-month confirmed disability progression analysis showed a 20% risk reduction but was not statistically significant, he said.

Remibrutinib also increased the proportion of patients achieving no evidence of disease activity, or NEDA-3, to 55%, with an odds ratio of 2.81, according to the presentation. The company reported reductions of 9% and 7% in neurofilament light, a blood biomarker associated with neural injury, across the two studies.

Safety profile and liver monitoring discussion

Wiendl said the pooled safety analysis showed no major differences in overall adverse events or infections between remibrutinib and teriflunomide. Discontinuations due to adverse events were lower with remibrutinib, according to the company.

Two deaths occurred in the remibrutinib arm: one from carbon monoxide poisoning on day three and one suicide at month 12 in a patient with prior psychiatric illness. Wiendl said both were considered unrelated to the investigational drug.

Bleeding events, a known consideration for the BTK inhibitor class, were predominantly minor skin manifestations that were transient and reversible, Wiendl said. He also highlighted lower rates of liver enzyme elevations versus teriflunomide and said no Hy’s Law cases were observed.

Nazem Atassi, Novartis’ global head of the neuroscience development unit, said more than 4,500 participants across 40 remibrutinib studies have received the drug at doses up to 600 mg. He added that Novartis has not identified a liver safety signal in more than 10,000 commercially treated patients in chronic spontaneous urticaria.

Atassi said Novartis does not expect routine liver monitoring to be required in the MS label, although final requirements will depend on discussions with regulators.

Commercial opportunity and development plans

Victor Bultó, president of Novartis U.S., said the company sees remibrutinib as a potential treatment for newly diagnosed patients, patients using oral MS therapies and patients switching from anti-CD20 treatments. Novartis estimates there are approximately 40,000 newly diagnosed relapsing MS patients annually in the U.S., 60,000 patients currently treated with oral therapies and 140,000 receiving anti-CD20 therapies.

The company estimates remibrutinib could become a more than $4 billion medicine in relapsing MS, with additional potential in non-relapsing secondary progressive MS. Bultó said Novartis still sees a more than $6 billion opportunity for Kesimpta and expects the two products can grow concurrently.

Novartis is recruiting patients for the Phase IIIb RESHAPE study, which evaluates switching from ocrelizumab to remibrutinib. The earliest readout is expected in 2028. The company is also recruiting the REMASTER Phase III trial in non-relapsing secondary progressive MS, with results expected in 2031.

Beyond MS, Novartis said remibrutinib is approved in chronic spontaneous urticaria and chronic inducible urticaria. Phase III studies are underway in hidradenitis suppurativa, with a 16-week readout expected in the fourth quarter of 2026, while a Phase III food-allergy study began in the third quarter of 2026 and is expected to report after 2029.

About Novartis (NYSE:NVS)

Novartis AG is a Switzerland-based pharmaceutical company focused on the discovery, development and commercialization of innovative medicines. The company's research and commercial activities span areas including cardiovascular, renal and metabolic diseases, immunology, neuroscience, oncology and hematology. Its portfolio includes prescription medicines such as Entresto, Cosentyx, Kisqali, Kesimpta, Leqvio, Pluvicto and Scemblix.

Novartis serves patients and healthcare providers in markets around the world.

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