GlobeNewswire by notified

Late-breaking data for Roche’s BTK inhibitor fenebrutinib show brain penetration and significant reduction in lesions in patients with relapsing multiple sclerosis

Share
  • New data from Phase II FENopta study in relapsing multiple sclerosis (RMS) show fenebrutinib crosses the blood-brain barrier with the potential to act directly on the chronic inflammation related to multiple sclerosis (MS)
  • More than 90% relative reduction in new/enlarging T2 lesions and new T1 gadolinium-enhancing (Gd+) lesions with fenebrutinib beginning at 8 weeks
  • The safety profile of fenebrutinib was consistent with previous and ongoing clinical trials across more than 2,500 people to date

Basel, 13 October 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced new data from the Phase II FENopta study showing that investigational, oral fenebrutinib is brain penetrant and reduces brain lesions in people with relapsing multiple sclerosis (RMS) with a consistent safety profile to other fenebrutinib trials. The late-breaking data were featured in an oral presentation at the 9th Joint ECTRIMS-ACTRIMS Meeting (European and Americas Committees for Treatment and Research in Multiple Sclerosis).

“These interesting results raise the possibility that fenebrutinib slows MS disease progression in part by acting directly within the brain,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “These data, which we are currently confirming in pivotal trials of both relapsing and progressive MS, suggest that fenebrutinib may have the potential to counteract acute and chronic inflammation within the brain to reduce disease activity in people with MS.”

Brain penetrance was measured by the level of fenebrutinib in the cerebrospinal fluid (CSF) of a subgroup of 11 patients with RMS. After 12 weeks of continuous treatment, the mean fenebrutinib concentration was 43.1 ng/mL. Similar fenebrutinib concentrations can produce near-maximal inhibition (IC90) in preclinical studies. Thus, the level of fenebrutinib in the brain and central nervous system may conceivably become high enough to reduce MS disease activity and progression in patients.

Fenebrutinib significantly reduced the total number of new T1 gadolinium-enhancing (T1 Gd+) brain lesions which are markers of active inflammation, and the total number of new or enlarging T2-weighted (T2) brain lesions, which represent the amount of disease burden or chronic lesion load. A rapid onset of lesion reduction was observed by 4 weeks, with relative reductions of 92% and 90% in T1 Gd+ lesions and relative reductions of 90% and 95% in T2 lesions observed at 8 and 12 weeks, respectively.

Furthermore, patients treated with fenebrutinib were four times more likely to be free from any new T1 Gd+ brain lesions and new or enlarging T2 brain lesions at weeks 4, 8, and 12 combined, compared to patients who received placebo (odds ratio 4.005, p=0.0117).

The safety profile of fenebrutinib was consistent with previous and ongoing fenebrutinib clinical trials across more than 2,500 people to date. There were no new safety concerns identified in the FENopta study. Overall rates of adverse events were 38% for fenebrutinib and 33% for placebo. The most common adverse events that were higher with fenebrutinib than placebo were abnormal liver enzyme levels (5.5% fenebrutinib, 0% placebo), headache (4.1% fenebrutinib, 2.8% placebo), nasopharyngitis (2.7% fenebrutinib, 0% placebo) and upper abdominal pain (2.7% fenebrutinib, 0% placebo).

Fenebrutinib is the only non-covalent and reversible BTK inhibitor in Phase III trials for MS and was designed to be highly selective, which may be important in reducing off-target effects of a molecule and potentially contribute to long-term safety outcomes. An open-label extension of FENopta is ongoing, with Phase III studies FENhance 1 and 2 currently enrolling patients with RMS and FENtrepid fully enrolled for patients with primary progressive MS (PPMS). Roche is committed to advancing innovative clinical research programmes to broaden the scientific understanding of MS, further reduce disability worsening in RMS and PPMS and improve the treatment experiences for those living with the disease.

About fenebrutinib
Fenebrutinib is an investigational oral, reversible and non-covalent Bruton’s tyrosine kinase (BTK) inhibitor that blocks the function of BTK. BTK, also known as tyrosine-protein kinase BTK, is an enzyme that regulates B-cell development and activation and is also involved in the activation of innate immune system myeloid lineage cells, such as macrophages and microglia. Preclinical data have shown fenebrutinib to be potent and highly selective, and it is the only reversible inhibitor currently in Phase III trials for MS. Fenebrutinib has been shown to be 130 times more selective for BTK vs. other kinases. These design features may be important as the high selectivity and reversibility can potentially reduce off-target effects of a molecule.

Fenebrutinib is a dual inhibitor of both B-cell and microglia activation. This dual inhibition may be able to reduce both MS disease activity and disability progression, thereby potentially addressing the key unmet medical need in people living with MS. The Phase III programme includes two identical trials in RMS (FENhance 1 & 2) with an active teriflunomide comparator and one trial in PPMS (FENtrepid) in which fenebrutinib is being evaluated against OCREVUS® (ocrelizumab). To date, more than 2,500 patients and healthy volunteers have been treated with fenebrutinib in Phase I, II and III clinical programmes across multiple diseases, including MS and other autoimmune disorders.

About the FENopta study
The FENopta study is a global Phase II, randomised, double-blind, placebo-controlled 12-week study to investigate the efficacy, safety and pharmacokinetics of fenebrutinib in 109 adults aged 18-55 years with RMS. The primary endpoint is the total number of new gadolinium-enhancing T1 lesions as measured by MRI scans of the brain at 4, 8 and 12 weeks. Secondary endpoints include the number of new or enlarging T2-weighted lesions as measured by MRI scans of the brain at 4, 8 and 12 weeks, and the proportion of patients free from any new gadolinium-enhancing T1 lesions and new or enlarging T2-weighted lesions as measured by MRI scans of the brain at 4, 8 and 12 weeks. The goal of the FENopta study is to characterise the effect of fenebrutinib on MRI and soluble biomarkers of disease activity and progression, and it includes an optional substudy to measure cerebrospinal fluid biomarkers of neuronal injury. Patients who complete the double-blind period are eligible for an open-label extension study.

About multiple sclerosis
Multiple sclerosis (MS) is a chronic disease that affects more than 2.8 million people worldwide. MS occurs when the immune system abnormally attacks the insulation and support around nerve cells (myelin sheath) in the central nervous system (brain, spinal cord and optic nerves), causing inflammation and consequent damage. This damage can cause a wide range of symptoms, including muscle weakness, fatigue and difficulty seeing, and may eventually lead to disability. Most people with MS experience their first symptom between 20 and 40 years of age, making the disease the leading cause of non-traumatic disability in younger adults.

People with all forms of MS experience disease progression – permanent loss of nerve cells in the central nervous system – from the beginning of their disease even if their clinical symptoms aren’t apparent or don’t appear to be getting worse. Delays in diagnosis and treatment can negatively impact people with MS, in terms of their physical and mental health, and contribute to the negative financial impact on the individual and society. An important goal of treating MS is to slow, stop and ideally prevent disease activity and progression as early as possible.

Relapsing-remitting MS (RRMS) is the most common form of the disease and is characterised by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. Approximately 85% of people with MS are initially diagnosed with RRMS. The majority of people who are diagnosed with RRMS will eventually transition to secondary progressive MS (SPMS), in which they experience steadily worsening disability over time. Relapsing forms of MS (RMS) include people with RRMS and people with SPMS who continue to experience relapses. Primary progressive MS (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 MS 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.

About Roche in Neuroscience
Neuroscience is a major focus of research and development at Roche. Our goal is to pursue ground-breaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases. Roche and Genentech are investigating more than a dozen medicines for neurological disorders, including MS, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, acute ischemic stroke, Duchenne muscular dystrophy and Angelman syndrome. 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.

In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work.

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 Relations
Phone: +41 61 688 8888 / e-mail: media.relations@roche.com

Hans Trees, PhD
Phone: +41 79 407 72 58
Nathalie Altermatt
Phone: +41 79 771 05 25

Simon Goldsborough
Phone: +44 797 32 72 915
Karsten Kleine
Phone: +41 79 461 86 83

Nina Mählitz
Phone: +41 79 327 54 74
Kirti Pandey
Phone: +49 172 6367262

Rebekka Schnell
Phone: +41 79 205 27 03
Sileia Urech
Phone: +41 79 935 81 48


Roche Investor Relations

Dr. Bruno Eschli
Phone: +41 61 68-75284
e-mail: bruno.eschli@roche.com
Dr. Sabine Borngräber
Phone: +41 61 68-88027
e-mail: sabine.borngraeber@roche.com

Dr. Birgit Masjost
Phone: +41 61 68-84814
e-mail: birgit.masjost@roche.com
Dr. Gerard Tobin
Phone: +41 61 68-72942
e-mail: gerard.tobin@roche.com


Investor Relations North America

Loren Kalm
Phone: +1 650 225 3217
e-mail: kalm.loren@gene.com

Attachment

To view this piece of content from www.globenewswire.com, please give your consent at the top of this page.
To view this piece of content from ml-eu.globenewswire.com, please give your consent at the top of this page.

About GlobeNewswire by notified

GlobeNewswire by notified
GlobeNewswire by notified
One Liberty Plaza - 165 Broadway
NY 10006 New York

https://notified.com

GlobeNewswire by notified is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.

Subscribe to releases from GlobeNewswire by notified

Subscribe to all the latest releases from GlobeNewswire by notified by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from GlobeNewswire by notified

Hexagon Purus receives order to deliver hydrogen distribution systems to a leading player within the green hydrogen ecosystem3.12.2023 21:57:00 CET | Press release

(Oslo, 3 December 2023) Hexagon Purus, a world leading manufacturer of zero emission mobility and infrastructure solutions, has received purchase orders for the delivery of hydrogen distribution systems to a leading player within the green hydrogen ecosystem, worth approximately EUR 9.6 million. Hexagon Purus’ hydrogen distribution systems, including its type 4 hydrogen cylinders, will be used to deliver green hydrogen to industrial applications in Central Europe. Driving Energy Transformation “There is a growing need to move hydrogen around, and our distribution systems are significantly more cost-effective than traditional metal tube transportation solutions. We expect demand for our systems to gain further momentum as green hydrogen increasingly becomes part of the hydrogen mix”, says Michael Kleschinski, EVP Hydrogen Infrastructure & Mobility at Hexagon Purus. About the market The industrial and mobility sectors account for close to 50% of annual carbon emissions globally, and hydr

Exhibition World Bahrain Secures "World’s Leading New Exhibition and Convention Centre 2023" Award at World Travel Awards 20233.12.2023 11:00:00 CET | Press release

DUBAI, United Arab Emirates, Dec. 03, 2023 (GLOBE NEWSWIRE) -- Exhibition World Bahrain (EWB), the Middle East’s newest and largest exhibition and convention centre, is proud to announce securing the “World’s Leading New Exhibition and Convention Centre 2023” at the World Travel Awards 2023. The award accolade was presented to Dr. Nasser Qaedi, the CEO of Bahrain Tourism and Exhibitions Authority (BTEA), during the World Travel Awards 2023 Grand Final Gala Ceremony, which took place at Burj Al Arab in Dubai, UAE, on December 1, 2023, in the presence of HE Philip Joseph Pierre, the prime minister of Saint Lucia, tourism ministers, and travel elites across the globe. Exhibition World Bahrain captured the highest number of votes, clinching the internationally recognised award from Bharat Mandapam, India, and Tākina Wellington Convention and Exhibition centre, New Zealand. With this unrivalled win, the Kingdom of Bahrain has further cemented its reputation as the leading global hub for the

Merus Presents Interim Data on MCLA-129 at ESMO Asia Congress 20233.12.2023 02:40:00 CET | Press release

MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC planned to initiate 1Q24 UTRECHT, The Netherlands and CAMBRIDGE, Mass., Dec. 02, 2023 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (“Merus”, “the Company”, “we”, or “our”), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics® and Triclonics®), today announced updated interim clinical data on MCLA-129 from ongoing expansion cohorts in non-small cell lung cancer (NSCLC) and in previously treated head and neck squamous cell carcinoma (HNSCC) were presented at the European Society for Medical Oncology (ESMO) Asia Congress 2023. “MCLA-129 is a very active drug in EGFRm NSCLC and we’re planning a focused investment to evaluate MCLA-129 in combination with chemotherapy, which we expect to start early in 2024,” said Bill Lundberg M.D., President, Chief Executive Officer of Merus. “We are in a fortunate position to have a strong balance sheet. We also recognize the importance of be

CASGEVY Gets Bahrain approval for treatment, marking it second country in the world2.12.2023 18:59:21 CET | Press release

MANAMA, Bahrain, Dec. 02, 2023 (GLOBE NEWSWIRE) -- Bahrain has become the second country in the world and the first in the Middle East to approve the use of CASGEVY (exagamglogene autotemcel) for the treatment of patients with sickle cell disease and transfusion-dependent beta-thalassemia. The treatment was developed by Vertex Pharmaceuticals and CRISPR Therapeutics, after conducting a series of successful clinical trials in the UK, US, France, Italy, and Germany, among others. Following the UK MHRA’s authorisation to use CASGEVY, Bahrain is the second country in the world and the first in the region to approve this treatment. This extraordinary development opens up new possibilities for medical advancements and reinforces Bahrain's commitment to pioneering healthcare solutions, offering a better quality of life for patients with these blood disorders. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a revolutionary gene-editing technique that holds immense potenti

Scatec at COP28: Accelerating renewable energy transition from Egypt to South Africa2.12.2023 14:01:22 CET | Press release

Dubai, 2 December 2023: This week, Scatec ASA, a leading renewable energy company, is actively engaging in the UN Climate Change Conference in Dubai (COP28). Our focus is to underscore renewable energy as an unequivocal solution to climate change and emphasise the critical need for increased green energy investments in emerging markets. COP28 serves as a pivotal platform for global stakeholders to reinforce commitments aimed at averting catastrophic consequences of climate change. Scatec aligns with climate experts in stressing the urgency of the situation and the imperative to continue advancing towards the objectives outlined in the Paris Agreement. There's no time to waste, and collective progress is crucial for safeguarding our planet's future. “We are at COP28 to highlight the key role renewable energy must play in our energy future, "At COP28, our focus is on underscoring the crucial role renewable energy must assume in shaping our energy future, particularly in emerging markets,