Fenebrutinib

iStock, wildpixel 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. One of the largest gatherings of multiple sclerosis researchers took place in Barcelona last month, as the space prepares to welcome a new class of treatment many believe will be a game-changer for patients. Bruton’s tyrosine kinase (BTK) inhibitors are expected by many in the pharmaceutical industry to be the next big breakthrough in MS, Andreas Muehler, co-founder and chief medical officer at Immunic Therapeutics, told BioSpace . A number of BTK inhibitors—oral small molecule drugs that block B cell signaling to reduce inflammation in both the central nervous and the peripheral immune systems—are currently moving through Phase III trials, most notably Sanofi’s tolebrutinib, which has an FDA target action date of Dec. 28. If approved, tolebrutinib will become the first BTK inhibitor for MS. Meanwhile, Roche is developing its own BTK inhibitor, fenebrutinib. The Swiss pharma presented data from the Phase II FENopta open-label extension trial at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) last month, showing “near-complete” suppression of disease activity in patients with relapsing MS at 96 weeks. These results were largely consistent with one-year data from the same trial presented last September. Roche currently has three Phase III trials underway in relapsing MS and primary-progressive MS. BTK inhibitors’ ability to cross the blood-brain barrier and penetrate the central nervous system (CNS) to slow neurodegeneration differentiates these treatments from biologics , which represent the top-selling drugs on the market. The ability to deliver these treatments orally could also allow for increased flexibility of dosing schedules compared to some current treatments that require injections. Anti-Inflammatory and Beyond Despite the high hopes for BTK inhibitors, safety concerns have created an environment of uncertainty around the class, according to industry watchers. Tolebrutinib and fenebrutinib have both been subject to partial clinical holds in the past three years due to cases of liver injury or indicated liver injury. This leaves the door open for other approaches, including one being pursued by Immunic. The New York and Germany–based biotech is progressing vidofludimus calcium, which activates the Nurr1 protein, through Phase III trials. When Immunic reported Phase II data from the asset in April, the biotech approached several companies about possible partnerships, “But this small industry group had decided that there is one mechanism of action, called BTK inhibitors, and that is the next big thing in MS,” Muehler said. “They believed that this type of drug would basically take care of all therapeutic needs in the space. We didn’t agree with that.” According to Muehler, the most common current approach to treating MS is to pursue anti-inflammatory actions because inflammation in the brain leads to lesions. Brain lesions are the hallmark of active disease and are used to diagnose and monitor MS. When Immunic began developing its lead candidate, this anti-inflammatory effect was the expected action of the drug. But when the biotech dug into its Phase II results, it saw the drug was having an effect beyond targeting inflammation, Muehler said. Further research revealed that vidofludimus calcium activated the Nurr1 protein—a mechanism associated with maintaining neuron health. Neurodegeneration occurs when levels of Nurr1 drop, he said. Since pregnancy tends to be protective against MS, Immunic consulted a study to understand which genes were up- or down-regulated by this state. The research identified four genes of interest, including NR4A2, which encodes Nurr1and found NR4A2 to be strongly activated, Muehler said. For Immunic, this meant the biotech had developed both an anti-inflammatory and a Nurr1 activator, which differentiates the drug from the other treatments that work solely through an anti-inflammatory effect. This is why Immunic is testing the candidate in patients with progressive MS, as this group generally responds poorly to anti-inflammatory therapies. This type of study may demonstrate that Nurr1 activation is neuroprotective, Muehler said. Results of this Phase II trial , announced in April, showed vidofludimus calcium reduced the relative risk of confirmed disability worsening events by 20% compared to placebo, with a 30% reduction in those patients with primary progressive MS. In an oral presentation at ECTRIMS last month, Immunic shared further data from the Phase II trial showing that vidofludimus calcium significantly increased the likelihood of 24-week confirmed disability improvement overall, with benefits observed in both primary progressive MS and non-active secondary progressive MS subgroups. If confirmed in Phase III studies, Muehler said a reduction in risk of worsening disability would be a landmark event for patients with progressive MS. On the Brink However, the long-term goal for MS research is to reverse disease progression or even discover a functional cure, Iain Greig, a reader in Medicinal Chemistry at the University of Aberdeen, told BioSpace in an email. An international research team, including Greig, recently received funding to develop a treatment that targets excitotoxicity, a process that harms nerve cells in people living with MS. By blocking this process, the researchers hope to encourage the body to rebuild myelin—the protective coating around nerves damaged in MS—and improve nerve recovery. Greig explained that should human trials validate the drug, it would be revolutionary in its ability to effectively reverse the disease. “Clearly, this is a dream scenario, but our pre-clinical data support this as a real possibility,” he said. “Alternatively, it may be that the nerve damage already sustained cannot be repaired even by remyelination, but reparation of the damaged myelin will prevent further neurodegeneration—thus ‘holding’ patients at an early ‘physically OK’ stage of the disease, as soon as they are diagnosed.” The research is currently in the final preclinical stages of validation. According to Greig, the team has funding to get through to IND-enabling studies. Beyond this, they are investigating all approaches to financing clinical trials, including seeking private investment and presenting their research to pharmaceutical companies. Back at ECTRIMS, University of Cambridge researchers presented Phase II clinical trial results indicating that a combination of metformin and clemastine showed potential to repair myelin. Previous evidence from animal studies suggested that metformin enhances the effect of clemastine on myelin repair, but until now, the two drugs had never been tested together in people. “My instinct is that we are on the brink of a new class of treatments to stop MS progression,” Nick Cunniffe, a clinical lecturer in neurology at the University of Cambridge, who led the CCMR-Two trial, said in an article published on the school’s research page, “and within the next decade we could see the first licensed treatment that repairs myelin and improves the lives of people living with MS.”

OCREVUS subcutaneous maintains consistent benefit-risk profile after two years New late-breaking data confirms OCREVUS significantly reduces disability progression in adults with advanced PPMSOne-year data reinforce that majority of infants potentially exposed to OCREVUS during pregnancy or breastfeeding exhibit antibody responsesFenebrutinib two-year Phase II data demonstrate near-complete suppression of disease activity at 96 weeks Basel, 24 September 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY) presents new data for OCREVUS® (ocrelizumab) and the investigational Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, Spain (24-26 September). New data show that treatment with OCREVUS provides significant benefit in preventing disability progression across diverse groups of people with multiple sclerosis (MS), including children with relapsing-remitting multiple sclerosis (RRMS), women with MS who are pregnant or breastfeeding, and adults with advanced primary progressive multiple sclerosis (PPMS). From Roche’s MS pipeline, Phase II data for fenebrutinib showing near-complete suppression of disease activity at 96 weeks will be presented ahead of upcoming pivotal study readouts. "We have made significant scientific progress in the treatment of MS and improving outcomes for people living with it, including key life moments such as planning for a family,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “With over a decade of efficacy and safety evidence, OCREVUS has transformed the course of MS for people with RMS and PPMS, and the new data further reinforce its role in preventing disability progression. We are also encouraged by the potential of fenebrutinib in redefining future treatment.” “ECTRIMS 2025 marks over a decade of scientific advancement since the first Phase III pivotal data from OCREVUS. The deepened understanding of B cells has led to breakthrough therapies that have revolutionised MS management by focusing on slowing disease progression,” said Professor Stephen L. Hauser, Director of the UCSF Weill Institute for Neurosciences. “While significant progress has been made, continued innovation focused on preventing both relapses and progression is essential to empowering people with MS to live life to the fullest. This year’s breadth of data demonstrates our collective commitment towards achieving these goals.” Two-year OCREVUS subcutaneous Phase III dataFinal data from the Phase III OCARINA II study show that OCREVUS subcutaneous (SC) injection maintains a consistent benefit-risk profile for up to two years, similar to the well-established OCREVUS intravenous infusion (IV), with continued near-complete suppression of relapses, brain lesion activity and disability progression. Phase IIIb OCREVUS results in broad PPMS populationThe ORATORIO-HAND expanded on the PPMS population studied in the registrational ORATORIO study by including older patients (age up to 65) and patients with advanced disability (Expanded Disability Status Scale [EDSS] score up to 8.0), for whom maintaining upper limb function is even more important for preserving quality of life and independence. OCREVUS shows 30% reduction in the risk of time to onset of 12-week composite confirmed disability progression (cCDP) in adults with advanced PPMS compared to placebo after a median 2.75 years of treatment (p=0.0007) in new late-breaking data from the Phase IIIb ORATORIO-HAND study. An even greater reduction of 55% in the risk of time to onset of 12-week cCDP was observed in patients with MRI lesion activity at baseline (p<0.0001). In a large PPMS population that included patients with more advanced disease, OCREVUS was superior to placebo in delaying overall disability progression (EDSS) and worsening of upper limb function (9-hole peg test). The safety profile of OCREVUS was consistent with previous studies, and no new safety signals were reported. OCREVUS is the first and only approved treatment for PPMS, and these data demonstrate that the benefit extends to patients with more advanced disease. Infant outcomes in pregnant and breastfeeding women treated with OCREVUSAn analysis of more than 5,000 pregnancies from the ocrelizumab pregnancy registry, the largest dataset of pregnancy outcomes for an anti-CD20 therapy in MS, will reinforce previous data that showed in-utero exposure to OCREVUS does not increase the risk of adverse pregnancy or infant outcomes. The majority of infants with potential OCREVUS exposure during pregnancy or breastfeeding exhibited meaningful antibody responses to childhood vaccines in one-year data from the Phase IV MINORE and SOPRANINO studies. Protective antibody responses to eight common vaccines given in the first year of life were observed in 86-100% of infants with potential exposure to OCREVUS during their mother’s pregnancy in MINORE and in 78-100% of infants with potential exposure to OCREVUS during breastfeeding in SOPRANINO. This means these children can recognise and fight the disease if encountered later, preventing severe illness and long-term harm. Infant B-cell levels also remained within normal range after 13 months in 95% (n=20/21) of infants in MINORE and 100% (n=11/11) of infants in SOPRANINO. Further data on the growth and development of infants with potential OCREVUS exposure during the first year of life will also be presented. OCREVUS in paediatric RRMSLate-breaking data from the Phase III OPERETTA 2 study investigating efficacy and safety of OCREVUS in children 10–17 years of age with RRMS will be presented on 26 September at 10:30 CEST. The OPERETTA 2 presentation will be the first time that data from the primary analysis of a pediatric-onset MS trial comparing a high-efficacy DMT (ocrelizumab) versus a globally approved treatment (fingolimod) will be shown. Also, long-term, 96-week results from the Phase II OPERETTA 1 paediatric study will be an oral presentation on 25 September at 15:15 CEST. Fenebrutinib two-year Phase II FENopta OLE resultsTwo-year data from the Phase II FENopta open-label extension (OLE) study will be presented, showing that patients with relapsing multiple sclerosis (RMS) treated with fenebrutinib maintained near-complete suppression of disease activity at 96 weeks. Patients enrolled in the OLE had a low annualised relapse rate (ARR) of 0.06, and during this time, there was no disability progression, as measured by the EDSS. At two years, MRI scans detected zero new T1 gadolinium-enhancing (T1-Gd+) lesions, which are markers of active inflammation. Neurofilament light chain, a marker of nerve cell damage, was decreased to healthy donor range in the first year and maintained in the second year of fenebrutinb treatment. Three Phase III clinical trials for fenebrutinib are ongoing, including the FENhance I and II studies in RMS and the FENtrepid study in PPMS. Initial data from the FENtrepid study are expected at the end of this year. In total, Roche will present 25 abstracts, including six oral and four late-breaking presentations at ECTRIMS 2025. Follow Roche on X via @Roche and keep up to date with ECTRIMS 2025 news and updates by using the hashtag #ECTRIMS2025. About OCREVUS® (ocrelizumab)OCREVUS is a humanised monoclonal antibody designed to target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. OCREVUS IV and OCREVUS subcutaneous (SC; marketed as OCREVUS ZUNOVO® [ocrelizumab hyaluronidase-ocsq] in the U.S.) are the only therapies approved for both RMS (including relapsing-remitting multiple sclerosis [RRMS] and active, secondary progressive multiple sclerosis [SPMS], as well as clinically isolated syndrome [CIS] in the U.S.) and primary progressive multiple sclerosis (PPMS). Both OCREVUS IV and SC are administered every six months. The initial IV dose is given as two 300 mg infusions two weeks apart with subsequent doses given as single 600 mg infusions. OCREVUS SC is given as a single 920 mg subcutaneous injection every six months. About fenebrutinibFenebrutinib is an investigational oral, central nervous system (CNS)-penetrant, reversible and non-covalent Bruton’s tyrosine kinase (BTK) inhibitor with an optimized pharmacokinetics (PK) profile. Fenebrutinib has been shown to be 130 times more selective for BTK vs. other kinases. Fenebrutinib is an inhibitor of both B-cell and microglia activation. This dual inhibition may be able to reduce both multiple sclerosis disease activity and disability progression, thereby potentially addressing the key unmet medical need of disability progression in people living with multiple sclerosis and providing comprehensive MS care. The fenebrutinib Phase III programme includes two identical trials in relapsing multiple sclerosis (RMS) (FENhance 1 & 2) with active comparator teriflunomide and the only trial in primary progressive multiple sclerosis (PPMS) (FENtrepid) in which a BTK inhibitor is being evaluated against OCREVUS. About multiple sclerosisMultiple sclerosis is a chronic disease that affects more than 2.9 million people worldwide. People with all forms of multiple sclerosis experience disease progression from the beginning of their disease. Therefore, an important goal of treating multiple sclerosis is to slow, stop and ideally prevent progression as early as possible. Approximately 85% of people with multiple sclerosis have a relapsing form of the disease (RMS) characterised by relapses and also worsening disability over time. Primary progressive multiple sclerosis (PPMS) is a debilitating form of the disease marked by steadily worsening symptoms but typically without distinct relapses or periods of remission. Approximately 15% of people with multiple sclerosis are diagnosed with the primary progressive form of the disease. Until the FDA approval of OCREVUS®, there had been no FDA-approved treatments for PPMS and OCREVUS is still the only approved treatment for PPMS. About Roche in NeuroscienceNeuroscience is a major focus of research and development at Roche. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases. Roche is investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Duchenne muscular dystrophy. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today. About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. All trademarks used or mentioned in this release are protected by law. Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Sileia UrechPhone: +41 79 935 81 48 Nathalie AltermattPhone: +41 79 771 05 25 Lorena CorfasPhone: +41 79 568 24 95 Simon GoldsboroughPhone: +44 797 32 72 915 Karsten KleinePhone: +41 79 461 86 83 Kirti PandeyPhone: +49 172 6367262 Yvette PetillonPhone: +41 79 961 92 50 Dr Rebekka SchnellPhone: +41 79 205 27 03 Attachment Media Release ECTRIMS English