Fenebrutinib

Novartis' oral BTK inhibitor Rhapsido (remibrutinib) has cleared its primary endpoints in two Phase III trials in relapsing multiple sclerosis (RMS), though the magnitude of benefit is weaker than some had hoped.The results may hand Roche's rival BTK candidate fenebrutinib an efficacy advantage, though Rhapsido could boast a cleaner safety profile in a drug class dogged by toxicity concerns.Full data from the REMODEL-1 and REMODEL-2 studies, toplined in September, were presented Friday at the MSToronto2026 conference and published simultaneously in The Lancet. Results showed Rhapsido reduced annualised relapse rates (ARRs) by 35.2% and 31.2% versus Sanofi's Aubagio (teriflunomide) in the two trials, respectively. Analysts had anticipated reductions of 45% to 60%.By contrast, fenebrutinib reduced ARRs by 51% and 59% versus Aubagio over a period of at least 96 weeks in the FENhance 1 and FENhance 2 trials. Novartis said ARRs in its studies were 0.073 and 0.080 with Rhapsido, compared to 0.112 and 0.116 with Aubagio, translating to "approximately one relapse every 13 years, without the need for chronic B-cell depletion," according to the company.Rhapsido also showed stronger effects on MRI measures, reducing new or enlarging T2 lesion activity by 65% and 70% across the respective REMODEL studies, while gadolinium-enhancing T1 lesions decreased by 66% in both.Meanwhile, a preplanned meta-analysis found that Rhapsido lowered the risk of six-month confirmed disability progression (6mCDP) by 29.2%, reaching nominal statistical significance. A 20.5% reduction at three months was not statistically significant.Analysts have been looking for evidence that BTK inhibitors can compete with established CD20-directed antibodies in MS, including Roche's Ocrevus (ocrelizumab), Novartis' Kesimpta (ofatumumab) and TG Therapeutics' Briumvi (ublituximab). In a recent FirstWord poll, nearly 60% of physicians said they viewed the anticipated role of BTK inhibitors as moderately significant, though they didn't anticipate an immediate shake-up in clinical practice (see – Physician Views Results: Neurologists express cautious optimism for BTK inhibitors in MS).US regulators recently accepted to review fenebrutinib in both relapsing and primary progressive MS, the latter indication backed by data from the Phase III FENtrepid trial, which pitted Rhapsido against Ocrevus.Liver safety may offer an advantage for Novartis' drug. Unlike fenebrutinib, whose development has been complicated by liver enzyme elevations and a reported Hy's Law case, Novartis said Rhapsido continues to show no liver safety signal in the REMODEL studies, including no Hy’s Law cases. ALT elevations exceeding 3x the upper limit of normal occurred in 2% of Rhapsido recipients versus 7.4% on Aubagio, while pooled analyses showed discontinuations due to adverse events were also lower at 3.1% versus 5.8%.Fred Lublin — professor of neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center — told FirstWord last month that if Rhapsido continues to show a cleaner liver safety profile than fenebrutinib, regulators may reconsider whether liver toxicity is a problem with all BTK inhibitors or only certain drugs in the class (see – KOL Views Q&A: Novartis takes tentative step towards differentiating remibrutinib among BTKs in MS).Novartis plans to seek global regulatory approvals for Rhapsido in RMS, with analysts forecasting peak sales exceeding $4 billion if the drug is approved for the indication. The drug is already approved for chronic spontaneous urticaria and symptomatic dermographism.FirstWord is currently fielding a poll to gauge physician responses to the detailed REMODEL-1 and REMODEL-2 data.

After disappointing Wall Street for most of 2026, Roche’s eye disease drug Vabysmo met analysts’ expectations for the first time this year. But the company may have bigger fish to fry heading into 2027. The bispecific antibody of VEGF-A and Ang-2 brought in 1.14 billion Swiss francs ($1.38 billion) in third-quarter sales, up 10% sequentially and topping consensus estimates by 2%. The beat comes as Vabysmo hit a milestone, having treated 1.5 million patients globally, Roche’s pharmaceuticals chief Teresa Graham told investors during a call Thursday. Vabysmo is a key driver in the 9% year-over-year sales growth at constant exchange rates for Roche’s ophthalmology franchise, as the drug continues market share gains, Graham said. Vabysmo is approved in the U.S. for wet age-related macular degeneration, diabetic macular edema and retinal vein occlusion. “By now, Vabysmo has established itself as the preferred first-line treatment, including in the U.S.,” she said. After stellar growth initially, Vabysmo suddenly lost momentum toward the end of 2025. Between the second-quarter 2025 and the second-quarter 2026, sales of the drug actually declined 1%. Roche previously attributed the deceleration to a reset of the U.S. branded VEGF market after the closure of certain charity copay programs. “I think the U.S. has re-baselined,” Graham said on Thursday’s call. “We are expecting to remain in that low single-digit growth for Vabysmo in terms of sales." “It’s probably important to note though that volume growth in the U.S. is much higher—there’s a contracting effect that takes effect here,” she continued. “And then, when you look ex-U.S., there is actually significant growth for Vabysmo, and more opportunity for growth and penetration to come outside of the U.S.” The Roche exec maintained that the current consensus peak sales outlook of 6 billion Swiss francs is “very reasonable,” and that Vabysmo is on track to achieve that. As the Vabysmo market stabilizes, Roche and investors are turning their attention to several potential blockbuster launches. The company’s oral SERD drug giredestrant is gearing up for an FDA decision by the end of November. For 2027, Roche is expecting FDA approvals for its KRAS G12C inhibitor divarasib in non-small cell lung cancer, for BTK inhibitor fenebrutinib in multiple sclerosis and sefaxersen in IgA nephropathy, among others. As Graham put it, Roche’s regulatory and launch teams will be “exceptionally busy” in the next few months. None of those will be easy rollouts. For giredestrant , the company is targeting a first-in-class adjuvant nod for early breast cancer, but as one analyst noted on the call, many doctors remain skeptical and are waiting for overall survival data to be convinced. The phase 3 lidERA trial supporting Roche’s filing will have another overall survival data cutoff toward the first half of 2027, Graham noted. As for another criticism around lidERA’s lack of involvement of a CDK4/6 inhibitor, Graham said that a single-arm sub-study in combination with Eli Lilly’s Verzenio is expected to read out this year. Roche recently also announced two new studies in the adjuvant setting, including an investigator-initiated study using a ctDNA-guided approach and a phase 1/3 testing giredestrant alongside Pfizer’s CDK4 candidate atirmociclib. For divarasib , Roche will need to compete with existing KRAS inhibitors, Amgen’s Lumakras and Bristol Myers Squibb’s Krazati. After seeing “strong” phase 3 data, to be presented at the European Society for Medical Oncology 2026 Congress this weekend, Roche has increased divarasib’s peak sales guidance to between 2 billion and 3 billion Swiss francs, Roche’s CEO Thomas Schinecker said on the call. In the BTK field, Roche’s fenebrutinib is on a collision course with Novartis’ Rhapsido in MS. It’s also not entirely clear how the oral BTK space will play out against antibody drugs such as Roche’s top-selling Ocrevus, although Graham argued fenebrutinib “will ultimately just crack up a whole new market segment,” rather than chipping away Ocrevus’ market. As for IgAN, the space has become crowded with multiple options across various mechanisms of action, including a new FDA nod Wednesday for AstraZeneca’s complement inhibitor Ultomiris. Despite the upcoming launches, one analyst on the call questioned Roche’s ability to maintain the same level of revenue growth in 2027, pointing to “growth pressures or slowdowns on a number of products.” In the first nine months of 2026, Roche’s pharmaceuticals division ginned up 36.2 billion Swiss francs ($44 billion) on the strength of a 7% year-over-year increase at constant exchange rates, and the entire group’s 46.5 billion Swiss francs marked 6% growth. “I can only say that we’re confident that we can maintain a similar momentum that we have,” Schinecker said on the call, adding that profit margins are expected to be “at least stable.”