Remibrutinib

iStock, Deagreez Novartis is planning to remibrutinib’s expanded approval in relapsing multiple sclerosis by next year, putting it just behind Roche’s own BTK inhibitor fenebrutinib. Novartis’ investigational BTK inhibitor remibrutinib, approved last September as Rhapsido for chronic spontaneous urticaria, reduced relapse and disease progression in two late-stage studies of relapsing multiple sclerosis. The positive results set the pharma up for an FDA filing next year and a potential face-off against Roche, which is nearing the market with its own BTK asset. Topline results from Novartis’ Phase 3 REMODEL-1 and REMODEL-2 studies, disclosed Tuesday morning , showed that patients on remibrutinib had lower annualized relapse rates than comparators on an active control, the multiple sclerosis (MS) drug teriflunomide. The drug is marketed by Sanofi Genzyme as Aubagio but is now available in generic form. Novartis’ drug also resulted in stronger reductions in inflammatory brain lesions. Remibrutinib likewise showed benefit on key secondary endpoints, including the progression of disability at three and six months, as per a pooled analysis of the two trials. Novartis did not provide specific numbers on the rate of improvement. “Remibrutinib is now the second BTK inhibitor to achieve nominal statistical significance in [disease progression] compared to teriflunomide” in pooled populations of relapsed MS patients, William Blair told investors in a Tuesday note. The other BTK inhibitor to hit this mark, the analysts said, is Roche’s fenebrutinib. At the 2026 meeting of the American Academy of Neurology in April, Roche touted a “ numerical reduction ” in scores on a scale that measures disease progression in patients who were given fenebrutinib, as compared with teriflunomide. At the time, the pharma also reported significant reductions in relapse rates and biomarkers of inflammation for fenebrutinib. Novartis on Tuesday didn’t provide specific data from the REMODEL trials but promised to do so at an upcoming medical meeting. “We view upcoming presentation of the REMODEL datasets as important to assessing [remibrutinib’s] competitiveness with fenebrutinib,” William Blair said on Tuesday. Novartis is planning to seek regulatory approval for remibrutinib for relapsing MS globally, slated for next year . Roche is likewise seeking clearance for fenebrutinib, with a filing planned for this year . Safety is likely to emerge as a key front in the battle between these two drugs, according to William Blair. “We expect comparison of remibrutinib and fenebrutinib’s safety pro be scrutinized,” the analysts said, particularly as the BTK inhibitor class continues to be hounded by liver safety questions . In late 2023, the FDA placed a partial clinical hold on fenebrutinib, citing cases of liver injury. It is unclear when the pause was lifted, but Roche has since continued development. Sanofi had also been advancing a BTK inhibitor, dubbed tolebrutinib, for MS—and has similarly been tripped up by safety issues. Cases of drug-induced liver injury prompted the FDA in mid-2022 to temporarily pause several Phase 3 trials for the drug. More recently, tolebrutinib in December 2025 failed a Phase 3 trial in primary progressive MS, forcing Sanofi to abandon regulatory aspirations in this subtype of the disease. The asset is no longer listed on Sanofi’s pipeline . Of note, Novartis on Tuesday emphasized that remibrutinib showed no concerning liver signals in the REMODEL studies. Multiple sclerosis Beyond BTK Inhibitors: Next Gen MS Treatments Could Transcend Symptom Management While Bruton’s tyrosine kinase inhibitors are often hailed as the next big breakthrough in multiple sclerosis, Immunic Therapeutics and others are leveraging neuroprotective targets and remyelination to keep the disease at bay. October 6, 2025 · 5 min read · Ben Hargreaves Read more

Novartis appears to have broken the curse of the BTK inhibitor class. The Swiss pharma announced Tuesday that two phase 3 trials for Rhapsido in relapsing multiple sclerosis hit their goals without any liver safety flags. The phase 3 Remodel-1 and -2 trials showed that Rhapsido (remibrutinib) beat Sanofi’s older drug Aubagio (teriflunomide) at reducing annualized relapse rate in relapsing MS, the studies’ primary endpoint, according to Novartis. The Novartis BTK drug also improved inflammatory brain lesions and demonstrated “clinically meaningful” reductions in secondary endpoints related to disability progression. A positive trend was observed in three-month confirmed disability progression, with nominal significance at the six-month mark in a preplanned combined analysis of the two identical trials. During an investor call in July, Novartis CEO Vas Narasimhan defined an improvement in disability progression in the “mid-teens” as clinically meaningful. But perhaps more importantly, Novartis said Rhapsido was well tolerated as the trials found “no liver safety signal, including no cases meeting Hy’s Law criteria,” which are used by doctors to identify patients at high risk of a fatal drug-induced liver injury. Nearly 2,000 patients participated in the two studies, in which patients were randomized 1:1 to receive either Rhapsido or Aubagio. Novartis plans to seek regulatory approval for Rhapsido in relapsing MS globally. Data from the two Remodel trials will be presented at MSToronto2026 in October. For years, the promise of the BTK inhibitor class in multiple sclerosis was undercut by recurring liver toxicity signals, which previously triggered FDA clinical holds on competing drugs from Sanofi and Roche. The concerns culminated in an FDA rejection for Sanofi’s tolebrutinib in non-relapsing secondary progressive MS, a form of the neurological disorder that involves a steady, continuous worsening of disability over time. In a complete response letter, the FDA specifically raised the risk of severe drug-induced liver injury recorded in tolebrutinib’s trials, including six cases that met Hy’s Law. As for Roche’s fenebrutinib, which was the subject of an FDA partial clinical hold in 2023 following two cases of elevated liver enzymes, the Swiss drugmaker recently reported one Hy’s Law case for its BTK drug and one for Aubagio in the phase 3 FENhance1 study in relapsing MS. “It’s also really important to note that since we put liver monitoring in place in the clinical trials, we have not seen any more cases,” Roche’s pharma chief, Teresa Graham, said during an investor call in January. “So I think we feel very good about the overall benefit-risk profile that we have with fenebrutinib, particularly when you consider the other half of that coin, which is the benefit.” In both FENhance1 and FENhance2, investigators saw eight deaths in the fenebrutinib arm, including two that were tied to the Roche BTK drug. There was one death (0.1%) among patients who took Aubagio. A Novartis spokesperson confirmed to Fierce that no treatment-related deaths were reported in the Remodel trials for Rhapsido. Rhapsido got its initial FDA approval in September 2025 as a treatment for chronic spontaneous urticaria (CSU), also known as chronic hives. In MS, Roche’s infused CD20 antibody Ocrevus has been the top-selling therapy, as Novartis’ self-injected CD20 drug Kesimpta plays catch up with fast sales growth. Now, with Rhapsido, Novartis aims to introduce a new oral option, potentially given ahead of biologics. “Despite advances in treatment, an unmet need remains for oral therapies that can deliver robust relapse prevention, slow disability progression, while maintaining a favorable safety profile,” Novartis’ chief medical officer, Shreeram Aradhye, said in a Sept. 1 statement. “The positive Remodel results underscore the potential of remibrutinib as a high-efficacy oral therapy for people living with RMS with a differentiated benefit-risk profile.” Besides annualized relapse rate and MRI performance, disability progression data will be important to determine where Rhapsido could be placed relative to the B-cell antibodies, Narasimhan said during the July investor call. Novartis is also testing its BTK drug in other forms of MS and other immune-related conditions. Besides MS and CSU, the company recently reported a positive pivotal readout for Rhapsido in chronic inducible urticaria and has launched a phase 3 in food allergy following promising mid-stage data, with a separate phase 3 ongoing in hidradenitis suppurativa. Tuesday’s announcement comes on the heels of the revelation of three deaths from Novartis’ investigational autoimmune CAR-T program, rapcabtagene autoleucel, in which patients died from complications caused by serious immune adverse reactions. As a result, Novartis has paused development of the CD19 candidate across multiple clinical studies, including a phase 1/2 involving relapsing MS patients.