主要目的：评价enpatoran在SCLE、DLE和/或SLE受试者中的长期安全性和耐受性。次要目的：评价enpatoran在SCLE、DLE和/或SLE受试者中的长期安全性和耐受性及疾病控制方面的长期有效性；第三/探索性目的：评价enpatoran在SCLE、DLE和/或SLE受试者中的疾病控制方面的长期有效性；评价enpatoran在SLE受试者中的疾病控制方面的长期有效性；评价enpatoran在SCLE、DLE和/或SLE受试者中对患者报告的症状和功能状态方面的长期有效性；评价enpatoran在活动性SLE受试者中对患者报告的症状和功能状态方面的长期有效性；研究活动性SLE受试者中，Enpatoran对生物标志物的影响；研究Enpatoran对免疫细胞亚群和免疫球蛋白的影响；研究Enpatoran对PD生物标志物的影响；通过稀疏PK采样采集enpatoran血浆浓度数据；评价enpatoran对疫苗免疫状态的长期影响。评价Enpatoran对比安慰剂对活动性狼疮皮疹受试者红斑的影响。

开始日期2023-03-16

申办/合作机构

R-Pharm Germany GmbH初创企业

[+3]

NCT05650567 / Recruiting临床2期

A Phase IIa, Randomized, Parallel, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Enpatoran in Dermatomyositis and Polymyositis Participants Receiving Standard of Care (NEPTUNIA)

The purpose of this study is to evaluate the efficacy and safety of orally administered M5049 in idiopathic inflammatory myopathies, specifically dermatomyositis (DM) and polymyositis (PM) participants for 24 weeks.

开始日期2023-01-19

申办/合作机构

EMD Serono Research & Development Institute, Inc.

[+1]

EUCTR2022-000239-21-BG / Unknown status临床2期

A Phase 2, Double-blind, Dose-Ranging, Parallel, Long-term Extension Study to Evaluate the Safety and Efficacy of Enpatoran in Participants with Subacute Cutaneous Lupus Erythematosus, Discoid Lupus Erythematosus and/or Systemic Lupus Erythematosus Having Completed the WILLOW (MS200569_0003) Study Treatment - WILLOW LTE

开始日期2022-10-18

申办/合作机构

Merck Healthcare KGaA

100 项与 Enpatoran 相关的临床结果

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100 项与 Enpatoran 相关的转化医学

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100 项与 Enpatoran 相关的专利（医药）

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项与 Enpatoran 相关的文献（医药）

2023-12-01·Clinical and Translational Science

Enpatoran in COVID‐19 pneumonia: Safety and efficacy results from a phase II randomized trial

Article

作者: Khursheed, Mukhy ; Roy, Sanjeev ; Santiaguel, Joel ; Klopp-Schulze, Lena ; Moreau, Flavie ; Shaw, Jamie ; Murta de Oliveira, Claudia ; Kao, Amy H ; Yu, Dongzi ; McKinnon, John E

Abstract:

Enpatoran is a selective inhibitor of toll‐like receptors 7 and 8 (TLR7/8) that potentially targets pro‐inflammatory pathways induced by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). A phase II study conducted in Brazil, the Philippines, and the USA during the early pandemic phase assessed the safety and efficacy of enpatoran in patients hospitalized with COVID‐19 pneumonia (NCT04448756). A total of 149 patients, who scored 4 on the World Health Organization's (WHO) 9‐point ordinal severity scale, were randomized 1:1:1 and received enpatoran 50 mg (n = 54) or 100 mg (n = 46), or placebo (n = 49) twice daily (b.i.d.) for 14 days plus standard of care. The primary objectives were safety and time to recovery (WHO 9‐point scale ≤3). Clinical deterioration (WHO 9‐point scale ≥ 5) was a key secondary objective. Treatment‐emergent adverse events (TEAEs) were comparable across groups (56.5%–63.0%). Treatment‐related TEAEs were numerically higher with enpatoran 50 mg (14.8%) than 100 mg (10.9%) or placebo (8.2%). Serious TEAEs were numerically lower with enpatoran (50 mg 9.3%, 100 mg 2.2%) than placebo (18.4%). The primary efficacy objective was not met; median time to recovery was 3.4–3.9 days across groups, with placebo‐treated patients recovering on average faster than anticipated. Clinical deterioration event‐free rates up to Day 7 were 90.6%, 95.6%, and 81.6% with enpatoran 50 mg, 100 mg, and placebo, respectively. Enpatoran was well tolerated by patients acutely ill and hospitalized with COVID‐19 pneumonia. Positive signals in some secondary end points suggested potential beneficial effects, supporting further evaluation of enpatoran in patients with hyperinflammation due to infection or autoimmunity.

2021-10-01·Pharmacology research & perspectives4区 · 医学

Phase 1 study in healthy participants of the safety, pharmacokinetics, and pharmacodynamics of enpatoran (M5049), a dual antagonist of toll‐like receptors 7 and 8

4区 · 医学

ArticleOA

作者: Strugala, Denis ; Mammasse, Nadra ; Bytyqi, Afrim ; Bachmann, Angelika ; Vetter, Claudia ; Klopp‐Schulze, Lena ; Port, Andreas ; Reh, Christian ; Ona, Victor ; Hussey, Elizabeth ; Shaw, Jamie V. ; Goteti, Kosalaram

Abstract:

This study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of enpatoran (formerly named M5049), a new toll‐like receptor (TLR) 7 and 8 dual antagonist, and the effect of food on a single dose in healthy participants. In this single phase 1, randomized (3:1), double‐blind, placebo‐controlled study, 96 participants received single and multiple ascending oral doses of enpatoran. Participants in single‐dose cohorts received one dose of enpatoran (1, 3, 9, 25, 50, 100, or 200 mg) or placebo using a sentinel dosing strategy. Multiple‐dose cohorts received enpatoran (9, 25, or 200 mg once daily, or 25 or 50 mg twice daily) or placebo for 14 days. Safety, tolerability, PK, and PD (ex vivo‐stimulated cytokine secretion) were assessed in both parts. The effect of food was assessed in an open‐label, one‐way crossover study in the 25 mg single‐dose cohort. Single‐ and multiple‐oral doses of enpatoran up to 200 mg were well tolerated and no significant dose‐limiting adverse events or safety signals were observed under fasting or fed conditions. PK parameters were linear and dose‐proportional across the dose range evaluated, with a slightly delayed absorption and lower peak concentration observed at 25 mg with food. Exposure‐dependent inhibition of ex vivo‐stimulated interleukin‐6 secretion was observed, with maximum inhibition at 200 mg. Enpatoran was well tolerated at doses up to 200 mg. Further investigation of enpatoran is warranted as a potential treatment for diseases driven by TLR7/8 overactivation, such as systemic lupus erythematosus and COVID‐19 pneumonia.

2021-03-01·The Journal of pharmacology and experimental therapeutics3区 · 医学

Discovery of M5049: A Novel Selective Toll-Like Receptor 7/8 Inhibitor for Treatment of Autoimmunity

3区 · 医学

Article

作者: Haselmayer, Philipp ; Okitsu, Shinji L ; Pereira, Albertina ; Musil, Djordje ; Walsky, Robert L ; Johnson, Theresa L ; Przetak, Melinda ; Deshpande, Aditee ; Morse, Noune Tahmassian ; Zimmerli, Simone C ; Vlach, Jaromir ; Tzvetkov, Evgeni ; Reissig, Sonja ; Bender, Andrew T ; Sherer, Brian

Toll-like receptor (TLR) 7 and TLR8 are transmembrane receptors that recognize single-stranded RNA. Activation of these receptors results in immune cell stimulation and inflammatory cytokine production, which is normally a protective host response. However, aberrant activation of TLR7/8 is potentially pathogenic and linked to progression of certain autoimmune diseases such as lupus. Thus, we hypothesize that an inhibitor that blocks TLR7/8 would be an effective therapeutic treatment. Prior efforts to develop inhibitors of TLR7/8 have been largely unsuccessful as a result of the challenge of producing a small-molecule inhibitor for these difficult targets. Here, we report the characterization of M5049 and compound 2, molecules which were discovered in a medicinal chemistry campaign to produce dual TLR7/8 inhibitors with drug-like properties. Both compounds showed potent and selective activity in a range of cellular assays for inhibition of TLR7/8 and block synthetic ligands and natural endogenous RNA ligands such as microRNA and Alu RNA. M5049 was found to be potent in vivo as TLR7/8 inhibition efficaciously treated disease in several murine lupus models and, interestingly, was efficacious in a disease context in which TLR7/8 activity has not previously been considered a primary disease driver. Furthermore, M5049 had greater potency in disease models than expected based on its in vitro potency and pharmacokinetic/pharmacodynamic properties. Because of its preferential accumulation in tissues, and ability to block multiple TLR7/8 RNA ligands, M5049 may be efficacious in treating autoimmunity and has the potential to provide benefit to a variety of patients with varying disease pathogenesis. SIGNIFICANCE STATEMENT: This study reports discovery of a novel toll-like receptor (TLR) 7 and TLR8 inhibitor (M5049); characterizes its binding mode, potency/selectivity, and pharmacokinetic and pharmacodynamic properties; and demonstrates its potential for treating autoimmune diseases in two mouse lupus models. TLR7/8 inhibition is unique in that it may block both innate and adaptive autoimmunity; thus, this study suggests that M5049 has the potential to benefit patients with autoimmune diseases.

项与 Enpatoran 相关的新闻（医药）

2023-07-18

·PRNewswire

Inflammatory Myositis Market to Accelerate Substantially at a CAGR of 11.7% by 2032, Predicts DelveInsight

The inflammatory myositis market is anticipated to surge owing to improvements in diagnosis over the globe and thus the surge in treatment options. In addition, the expected launch of emerging therapies by leading companies such as CSL Behring, Immunoforge Co. Ltd., Argenx, Janssen, Abcuro, Inc., and others will also propel the inflammatory myositis market size. LAS VEGAS, July 18, 2023 /PRNewswire/ -- DelveInsight's Inflammatory Myositis Market Insights report includes a comprehensive understanding of current treatment practices, inflammatory myositis emerging drugs, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU-4 (Italy, Spain, France, and Germany), the United Kingdom, and Japan]. Key Takeaways from the Inflammatory Myositis Market Report As per DelveInsight analysis, the inflammatory myositis market size in the 7MM was approximately USD 575 million in 2022. According to the assessment done by DelveInsight, the estimated total diagnosed prevalent inflammatory myositis cases in the 7MM were approximately 184K in 2022. Leading inflammatory myositis companies such as CSL Behring, Immunoforge Co. Ltd., Argenx, Janssen, Abcuro, Inc., Horizon Therapeutics, Merck KGaA, Galapagos NV, Priovant Therapeutics, Roivant, Alexion Pharmaceuticals, Pfizer, Kezar Life Sciences, and others are developing novel inflammatory myositis drugs that can be available in the inflammatory myositis market in the coming years. The promising inflammatory myositis therapies in the pipeline include Hizentra, PF 1801, Efgartigimod, Nipocalimab, ABC008, Daxdilimab (HZN-7734/MEDI7734/VIB7734), Enpatoran (M5049), GLPG3667, Brepocitinib (PF-06700841), ULTOMIRIS (Ravulizumab), PF-06823859 (Dazukibart), Zetomipzomib (KZR-616), and others. Discover which therapies are expected to grab the major inflammatory myositis market share @ Inflammatory Myositis Market Report Inflammatory Myositis Overview Inflammatory myositis, often known as myositis, is a rare autoimmune condition characterized by muscular inflammation. Polymyositis, dermatomyositis, inclusion body myositis, and necrotizing autoimmune myopathy are all examples of inflammatory myositis. The exact cause of inflammatory myositis is unknown, although it is thought to be related to an aberrant immunological response in which the body's immune system destroys its own muscle tissue by mistake. Muscle weakness, muscle soreness, difficulty swallowing, weariness, and, in certain cases, skin rashes are the most common symptoms of inflammatory myositis. The severity of the inflammatory myositis symptoms varies and may worsen over time. Dermatomyositis is characterized by skin rashes, which frequently include the face and upper torso. A medical history, physical examination, blood tests, electromyography (EMG), muscle biopsy, and imaging techniques such as MRI are commonly used to identify inflammatory myositis. Inflammatory Myositis Epidemiology Segmentation DelveInsight estimates that there were approximately 184K diagnosed prevalent cases of inflammatory myositis in the 7MM in 2022. According to DelveInsight estimates, assessments indicate that within the age groups of 0–17 years, 18–44 years, 45–64 years, and 65 years and above, a greater prevalence of diagnosed cases of inflammatory myositis was observed among individuals aged 45–64 years with 77.6K cases in 2022 in the 7MM. The inflammatory myositis market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into: Total Inflammatory Myositis Diagnosed Prevalent Cases Inflammatory Myositis Type-specific Cases Inflammatory Myositis Age-specific Diagnosed Prevalent Cases Inflammatory Myositis Gender-specific Diagnosed Prevalent Cases Inflammatory Myositis Treatment Market Inflammatory myositis is usually treated with a mix of pharmaceutical treatments and supportive measures. The primary goals of inflammatory myositis treatment are to reduce inflammation, manage symptoms, preserve muscle function, and avoid potential consequences. Currently, therapeutic techniques for inflammatory myositis include a combination of immunosuppressive medications such as corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) such as immunosuppressive agents. Biologic drugs, physical therapy, and supportive measures are also used. Biologic drugs such as rituximab or tocilizumab, which precisely targets immune system components to decrease inflammation, may be used in patients with severe or resistant inflammatory myositis.In more severe or resistant cases, drugs such as cyclophosphamide or cyclosporine may be administered to dampen the immune response and reduce inflammation. If corticosteroids, immunosuppressive drugs, and IVIG fail to relieve symptoms, IV cyclophosphamide can be used as a last-resort treatment. Prograf capsules (generic name: tacrolimus) are an immunosuppressive medicine extensively used in the treatment of a variety of medical diseases, including myositis, in Japan. The US Food and Drug Administration (FDA) has approved OCTAGAM 10% (Immune Globulin Intravenous [Human]) for the treatment of adult dermatomyositis, a rare immune-mediated inflammatory disease. The US FDA has approved ACTHAR Gel (repository corticotropin injection) for use in individuals with two subtypes of idiopathic inflammatory myopathies (IIMs), dermatomyositis (DM) and polymyositis (PM). ACTHARGel is a naturally occurring blend of adrenocorticotropic hormone analogues and pituitary peptides. To know more about inflammatory myositis treatment, visit @ Inflammatory Myositis Treatment Drugs Key Inflammatory Myositis Therapies and Companies Hizentra: CSL Behring PF 1801: Immunoforge Co. Ltd. Efgartigimod: Argenx Nipocalimab: Janssen ABC008: Abcuro, Inc. Daxdilimab (HZN-7734/MEDI7734/VIB7734): Horizon Therapeutics Enpatoran (M5049): Merck KGaA GLPG3667: Galapagos NV Brepocitinib (PF-06700841): Priovant Therapeutics/Roivant ULTOMIRIS (Ravulizumab): Alexion Pharmaceuticals PF-06823859 (Dazukibart): Pfizer Zetomipzomib (KZR-616): Kezar Life Sciences Learn more about the FDA-approved drugs for inflammatory myositis @ Drugs for Inflammatory Myositis Treatment Inflammatory Myositis Market Dynamics The inflammatory myositis market is expected to change in the coming years. The therapeutic landscape is abundant in terms of assessing the efficacy, safety, and tolerability of innovative medications in patients with inflammatory myositis and its different forms. Rising data on the general prevalence of inflammatory myositis and its subtypes is predicted to dramatically increase the patient pool. Moreover, the inflammatory myositis companies and academics are working to assess challenges and seek opportunities that could influence inflammatory myositis R&D. The therapies under development are focused on novel approaches to treat/improve the disease condition. Inflammatory myositis companies are involved in developing inflammatory myositis therapies. Moreover, the anticipated introduction of emerging therapies with improved efficacy and a further improvement in the diagnosis rate are expected to drive the growth of the inflammatory myositis market in the 7MM. However, certain factors may affect the growth of the inflammatory myositis market. The growing pipeline is gloomy, with a scarcity of effective late-stage drugs. The existing therapeutic options are linked with concerning side effects such as renal toxicity, nausea, osteoporosis, pulmonary toxicity, and others. Moreover, the inflammatory myositis market growth may be offset by unaffordable pricing, market access and reimbursement issues, and a shortage of healthcare specialists. In addition, the undiagnosed, unreported cases and the unawareness about the disease may also impact the inflammatory myositis market growth. Scope of the Inflammatory Myositis Market Report Therapeutic Assessment: Inflammatory Myositis current marketed and emerging therapies Inflammatory Myositis Market Dynamics: Attribute Analysis of Emerging Inflammatory Myositis Drugs Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's Views, Analyst's Views, Inflammatory Myositis Market Access and Reimbursement Discover more about inflammatory myositis drugs in development @ Inflammatory Myositis Clinical Trials Table of Contents Related Reports Myositis Pipeline Myositis Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key myositis companies, including GlaxoSmithKline, Corbus Pharmaceuticals, Abcuro, Inc., Orphazyme, Bristol-Myers Squibb, Kezar Life Sciences, Inc., Horizon Therapeutics, Viela Bio, Paean Biotechnology Inc., Alexion Pharmaceuticals, Janssen Biotech, CSL Behring, Pfizer, Roche, among others. Inclusion Body Myositis Epidemiology Forecast Inclusion Body Myositis Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted inclusion body myositis epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Inclusion Body Myositis Market Inclusion Body Myositis Market Insight, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key inclusion body myositis companies, including Acceleron Pharma Inc, KPI Therapeutics Inc, Milo Biotechnology LLC, Nobelpharma Co Ltd, Orphazyme ApS, Ultragenyx Pharmaceutical Inc, among others. Inclusion Body Myositis Pipeline Inclusion Body Myositis Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key inclusion body myositis companies, including Acceleron Pharma Inc, KPI Therapeutics Inc, Milo Biotechnology LLC, Nobelpharma Co Ltd, Orphazyme ApS, Ultragenyx Pharmaceutical Inc, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

上市批准

2022-11-21

·Business Wire

Merck Aims to Double R&D Productivity in Oncology, Neurology and Immunology to Deliver More Medicines to Patients Faster

DARMSTADT, Germany--( BUSINESS WIRE )--Merck, a leading science and technology company, today shared updates on the company’s healthcare research and development strategy, aimed at doubling R&D productivity. To achieve the goal of introducing one new product or major indication every 1.5 years on average, the company will focus its expertise and capabilities and leverage synergies within the existing pipeline to deliver transformative medicines in Oncology, Neurology and Immunology, augmented by an increased focus on external innovation. The company expects to maintain the output of its internal discovery engine, while more than 50% of future launches will result from external co-development partnerships and strategic in-licensing of assets for further in-house development. The strategy was shared today at the company’s R&D Update Call. “We are driven by our ambition to accelerate the discovery, development and delivery of innovative medicines to patients with cancer and neuroinflammatory and immune-mediated diseases,” said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business sector of Merck. “With a mindset of design simplicity and resource discipline paired with agility of execution, we will speed the generation of high-quality data that will support our efforts to bring forth more medicines for more patients, faster.” To increase R&D productivity, the company will build on its established expertise in the underlying biology of its focused therapeutic areas of oncology, neurology and immunology and will leverage technological capabilities, particularly its industry-leading antibody-drug conjugate (ADC) technology. Oncology: Synergistic Approaches to Striking Cancer at Its Core The company’s oncology research and development strategy centers on cancer DNA while building on existing leadership in key cancer types, including head and neck, urothelial and colorectal cancers. The oncology pipeline is focused on synergistic approaches targeting key pathways involved in cancer cell survival, deploying mechanisms to hit cancer at its core: Delivering tumor DNA-damaging payloads right to the cancer with cutting-edge ADC technology Preventing cancer cells from repairing DNA damage, through inhibition of the DNA damage response (DDR) Restoring sensitivity to apoptosis, the cells’ natural death mechanism, which cancer can inhibit The lead asset in the oncology pipeline is xevinapant, an investigational first-in-class potent oral small molecule IAP (Inhibitor of Apoptosis Protein) inhibitor being evaluated in the curative setting of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN)—an area that has not seen significant advances in treatment in the past 20 years. Xevinapant, which was in-licensed from Debiopharm in March 2021, builds on the company’s long heritage and extensive expertise in SCCHN. Based on the promising efficacy and safety profile seen in the Phase II trial and the urgent need for new treatments, the company is evaluating xevinapant in two ongoing randomized, double-blind, placebo-controlled Phase III clinical trials with the goal of transforming the standard of care: the TrilynX study (NCT04459715) in patients with unresected LA SCCHN, and the XRay Vision study (NCT05386550) in patients with resected LA SCCHN who are at high risk of relapse and are ineligible for cisplatin. Additional external studies and real-world evidence are expected to elucidate the potential for xevinapant across additional patient segments. The company’s broad portfolio of selective and potent DDR inhibitors includes several agents under development that directly inhibit DDR pathways required for cancer cell survival. By attacking the inherent genetic instability of cancer cells, these agents have the potential to exploit this weakness and tip the therapeutic balance in difficult-to-treat cancers. The oral ATR (ataxia telangiectasia and Rad3-related) inhibitor M1774, which has been designed as a potentially best-in-class molecule, is the leading DDR asset in the pipeline. Recently presented dose-escalation results showed that M1774 at its recommended dose expansion level showed pharmacologically robust exposure and a favorable safety profile. M1774 has broad potential in combination with other DDR inhibitors and other medicines, and as monotherapy in the right genomic context. The DDR portfolio also includes inhibitors of ATM (ataxia-telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase) and has recently been complemented by a collaboration with Nerviano Medical Sciences with the option for a license agreement on the next-generation selective PARP1 (poly (ADP-ribose) polymerase) inhibitor NMS-293. Earlier this year, M9140, the first ADC developed using the company’s own technology, advanced into human trials. The ongoing Phase Ia study is assessing M9140 in patients with colorectal cancer. M9140 is an anti-CEACAM5 ADC with a topoisomerase 1 inhibitor (exatecan) payload that has been rationally designed for stability in circulation and superior cancer cell killing activity with a broad therapeutic window. M9140 has synergistic potential with DDR inhibition as well. Neurology and Immunology: Expansion Building on Strength in Neurology and Immune Biology In neurology and immunology, Merck aims to expand its multiple sclerosis (MS) portfolio with evobrutinib, an investigational, oral, CNS-penetrating, highly selective inhibitor of Bruton’s tyrosine kinase (BTK) with the potential to become a best-in-class treatment option for relapsing multiple sclerosis (RMS). In a Phase II study and follow-up, evobrutinib is the first BTK inhibitor (BTKi) to demonstrate sustained clinical efficacy for people with RMS through three and a half years and impact early biomarkers of ongoing central inflammation that correlate with disease progression, including slowly expanding lesions volume and levels of blood neurofilament light chain protein. In pre-clinical studies, evobrutinib modulated both B cells and macrophages (in the periphery)/microglia (in the brain). This approach has the potential to positively impact both progression caused by relapses and silent progression occurring independent of relapse. During Phase II, the BTKi dose-finding study demonstrated that BID dosing achieved maximal efficacy with >95% BTK occupancy maintained in 98% of patients before the next dose. The Phase III readout for evobrutinib is expected in Q4 2023. Merck also seeks to expand in neurology by evaluating the potential of oral cladribine in neurological diseases where inflammation is a primary driver, such as generalized myasthenia gravis. The company is looking to diversify the pipeline with immunology and accelerate R&D by focusing on targets with proven biology via novel modalities. Key to these efforts is the ongoing Phase II WILLOW study of the TLR7/8 inhibitor enpatoran in cutaneous and systemic lupus erythematosus. Building on expertise in neurology, the company is initiating a proof-of-concept study in neuromuscular conditions dermatomyositis and polymyositis with enpatoran in 2023. These conditions have a high unmet medical need characterized by progressive muscle weakness and show lupus-like patterns of immune activation and TLR7/8 expression. “Patients rely on us. By building on our existing strengths and maximizing synergies within our in-house discovered pipeline and with external assets, we will secure sustainable R&D productivity that leads to innovative medicines for patients in need,” Bar-Zohar added. To access the presentation and a recording, please visit the company’s website at https://www.merckgroup.com/en/investors/events-and-presentations.html All Merck press releases are distributed by e-mail at the same time they become available on the Merck website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service. About Merck Merck, a leading science and technology company, operates across life science, healthcare and electronics. More than 60,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2021, Merck generated sales of € 19.7 billion in 66 countries. Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as MilliporeSigma in life science, EMD Serono in healthcare, and EMD Electronics in electronics.

临床2期临床1期临床结果临床3期引进/卖出

2022-11-21

·BioSpace

Merck KGaA, Darmstadt, Germany Aims to Double R&D Productivity in Oncology, Neurology and Immunology to Deliver More Medicines to Patients Faster

Company aims to launch one new product or indication every 1.5 years on average, bolstered by external innovation Phase III assets xevinapant and evobrutinib are expected to drive next wave of launches Focused leadership approach to pipeline enrichment builds on expertise in key biology and therapeutic areas as well as technological capabilities Not intended for UK-based media DARMSTADT, Germany--(BUSINESS WIRE)-- Merck KGaA, Darmstadt, Germany, a leading science and technology company which operates its Healthcare business as EMD Serono in the US and Canada, today shared updates on the company’s healthcare research and development strategy, aimed at doubling R&D productivity. To achieve the goal of introducing one new product or major indication every 1.5 years on average, the company will focus its expertise and capabilities and leverage synergies within the existing pipeline to deliver transformative medicines in Oncology, Neurology and Immunology, augmented by an increased focus on external innovation. The company expects to maintain the output of its internal discovery engine, while more than 50% of future launches will result from external co-development partnerships and strategic in-licensing of assets for further in-house development. The strategy was shared today at the company’s R&D Update Call. “We are driven by our ambition to accelerate the discovery, development and delivery of innovative medicines to patients with cancer and neuroinflammatory and immune-mediated diseases,” said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business sector of Merck KGaA, Darmstadt, Germany. “With a mindset of design simplicity and resource discipline paired with agility of execution, we will speed the generation of high-quality data that will support our efforts to bring forth more medicines for more patients, faster.” To increase R&D productivity, the company will build on its established expertise in the underlying biology of its focused therapeutic areas of oncology, neurology and immunology and will leverage technological capabilities, particularly its industry-leading antibody-drug conjugate (ADC) technology. Oncology: Synergistic Approaches to Striking Cancer at Its Core The company’s oncology research and development strategy centers on cancer DNA while building on existing leadership in key cancer types, including head and neck, urothelial and colorectal cancers. The oncology pipeline is focused on synergistic approaches targeting key pathways involved in cancer cell survival, deploying mechanisms to hit cancer at its core: Delivering tumor DNA-damaging payloads right to the cancer with cutting-edge ADC technology Preventing cancer cells from repairing DNA damage, through inhibition of the DNA damage response (DDR) Restoring sensitivity to apoptosis, the cells’ natural death mechanism, which cancer can inhibit The lead asset in the oncology pipeline is xevinapant, an investigational first-in-class potent oral small molecule IAP (Inhibitor of Apoptosis Protein) inhibitor being evaluated in the curative setting of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN)—an area that has not seen significant advances in treatment in the past 20 years. Xevinapant, which was in-licensed from Debiopharm in March 2021, builds on the company’s long heritage and extensive expertise in SCCHN. Based on the promising efficacy and safety pro in the Phase II trial and the urgent need for new treatments, the company is evaluating xevinapant in two ongoing randomized, double-blind, placebo-controlled Phase III clinical trials with the goal of transforming the standard of care: the TrilynX study (NCT04459715) in patients with unresected LA SCCHN, and the XRay Vision study (NCT05386550) in patients with resected LA SCCHN who are at high risk of relapse and are ineligible for cisplatin. Additional external studies and real-world evidence are expected to elucidate the potential for xevinapant across additional patient segments. The company’s broad portfolio of selective and potent DDR inhibitors includes several agents under development that directly inhibit DDR pathways required for cancer cell survival. By attacking the inherent genetic instability of cancer cells, these agents have the potential to exploit this weakness and tip the therapeutic balance in difficult-to-treat cancers. The oral ATR (ataxia telangiectasia and Rad3-related) inhibitor M1774, which has been designed as a potentially best-in-class molecule, is the leading DDR asset in the pipeline. Recently presented dose-escalation results showed that M1774 at its recommended dose expansion level showed pharmacologically robust exposure and a favorable safety profile. M1774 has broad potential in combination with other DDR inhibitors and other medicines, and as monotherapy in the right genomic context. The DDR portfolio also includes inhibitors of ATM (ataxia-telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase) and has recently been complemented by a collaboration with Nerviano Medical Sciences with the option for a license agreement on the next-generation selective PARP1 (poly (ADP-ribose) polymerase) inhibitor NMS-293. Earlier this year, M9140, the first ADC developed using the company’s own technology, advanced into human trials. The ongoing Phase Ia study is assessing M9140 in patients with colorectal cancer. M9140 is an anti-CEACAM5 ADC with a topoisomerase 1 inhibitor (exatecan) payload that has been rationally designed for stability in circulation and superior cancer cell killing activity with a broad therapeutic window. M9140 has synergistic potential with DDR inhibition as well. Neurology and Immunology: Expansion Building on Strength in Neurology and Immune Biology In neurology and immunology, Merck KGaA, Darmstadt, Germany, aims to expand its multiple sclerosis (MS) portfolio with evobrutinib, an investigational, oral, CNS-penetrating, highly selective inhibitor of Bruton’s tyrosine kinase (BTK) with the potential to become a best-in-class treatment option for relapsing multiple sclerosis (RMS). In a Phase II study and follow-up, evobrutinib is the first BTK inhibitor (BTKi) to demonstrate sustained clinical efficacy for people with RMS through three and a half years and impact early biomarkers of ongoing central inflammation that correlate with disease progression, including slowly expanding lesions volume and levels of blood neurofilament light chain protein. In pre-clinical studies, evobrutinib modulated both B cells and macrophages (in the periphery)/microglia (in the brain). This approach has the potential to positively impact both progression caused by relapses and silent progression occurring independent of relapse. During Phase II, the BTKi dose-finding study demonstrated that BID dosing achieved maximal efficacy with >95% BTK occupancy maintained in 98% of patients before the next dose. The Phase III readout for evobrutinib is expected in Q4 2023. Merck KGaA, Darmstadt, Germany, also seeks to expand in neurology by evaluating the potential of oral cladribine in neurological diseases where inflammation is a primary driver, such as generalized myasthenia gravis. The company is looking to diversify the pipeline with immunology and accelerate R&D by focusing on targets with proven biology via novel modalities. Key to these efforts is the ongoing Phase II WILLOW study of the TLR7/8 inhibitor enpatoran in cutaneous and systemic lupus erythematosus. Building on expertise in neurology, the company is initiating a proof-of-concept study in neuromuscular conditions dermatomyositis and polymyositis with enpatoran in 2023. These conditions have a high unmet medical need characterized by progressive muscle weakness and show lupus-like patterns of immune activation and TLR7/8 expression. “Patients rely on us. By building on our existing strengths and maximizing synergies within our in-house discovered pipeline and with external assets, we will secure sustainable R&D productivity that leads to innovative medicines for patients in need,” Bar-Zohar added. To access the presentation and a recording, please visit the company’s website at All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group website. In case you are a resident of the USA or Canada, please go to to register for your online, change your selection or discontinue this service. About Merck KGaA, Darmstadt, Germany Merck KGaA, Darmstadt, Germany, a leading science and technology company, operates across life science, healthcare and electronics. More than 60,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2021, Merck KGaA, Darmstadt, Germany, generated sales of € 19.7 billion in 66 countries. The company holds the global rights to the name and trademark “Merck” internationally. The only exceptions are the United States and Canada, where the business sectors of Merck KGaA, Darmstadt, Germany, operate as MilliporeSigma in life science, EMD Serono in healthcare and EMD Electronics in electronics. Since its founding in 1668, scientific exploration and responsible entrepreneurship have been key to the company’s technological and scientific advances. To this day, the founding family remains the majority owner of the publicly listed company.

临床2期临床3期临床1期临床结果

100 项与 Enpatoran 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
皮肌炎	临床2期	美国	EMD Serono Research & Development Institute, Inc.	2023-01-19
皮肌炎	临床2期	捷克	EMD Serono Research & Development Institute, Inc.	2023-01-19
皮肌炎	临床2期	希腊	EMD Serono Research & Development Institute, Inc.	2023-01-19
皮肌炎	临床2期	意大利	EMD Serono Research & Development Institute, Inc.	2023-01-19
皮肌炎	临床2期	波兰	EMD Serono Research & Development Institute, Inc.	2023-01-19
皮肌炎	临床2期	西班牙	EMD Serono Research & Development Institute, Inc.	2023-01-19
皮肌炎	临床2期	英国	EMD Serono Research & Development Institute, Inc.	2023-01-19
盘状红斑狼疮	临床2期	美国	Merck Healthcare KGaA	2022-02-14
盘状红斑狼疮	临床2期	美国	默克雪兰诺（北京）医药研发有限公司	2022-02-14
盘状红斑狼疮	临床2期	美国	R-Pharm Germany GmbH初创企业	2022-02-14

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ACR2022 人工标引	临床1期	-	36	Enpatoran	鏇憲襯鏇網遞鹽簾憲窪(淵構鑰構憲鹽餘醖襯獵) = Cmax: 0.9409 [0.7855–1.1270]; AUC0-inf: 0.8959 [0.7497–1.0704] and AUC0-tlast: 0.8963 [0.7511–1.0695]). 糧選鹹築觸艱鏇鑰網醖 (製窪範壓構積窪衊觸遞 ) 更多	积极	2022-09-12
NCT04448756 (CTgov)	临床2期	新型冠状病毒感染	149	placebo (Placebo)	簾網鹽夢衊膚鏇淵淵憲(蓋淵繭鹽積齋餘鏇遞壓) = 獵艱醖鬱簾製餘醖網襯窪壓選鹽範遞襯膚鹹積 (積網顧獵鑰範壓鹹簾獵, 憲選憲觸範鏇壓廠糧獵 ~ 齋鏇遞顧鏇淵製積鑰膚) 更多	-	2022-06-06
				M5049 (M5049 100 mg)	簾網鹽夢衊膚鏇淵淵憲(蓋淵繭鹽積齋餘鏇遞壓) = 製鬱鹽顧選顧蓋齋衊簾窪壓選鹽範遞襯膚鹹積 (積網顧獵鑰範壓鹹簾獵, 築衊蓋膚鹹積鑰簾遞廠 ~ 顧觸鹽鏇網簾積醖築鏇) 更多
NCT04448756 (ANEMONE, EULAR2022)	临床2期	新型冠状病毒感染 cytokines \| C-reactive protein \| D-dimer ... 更多	149	Enpatoran 50 mg BID	淵構壓觸襯膚餘願窪選(膚獵積壓選齋積餘蓋糧) = 觸蓋鬱壓淵廠選窪築窪獵選積鏇構選淵構鹽遞 (範鹹選遞製構顧廠鬱艱 ) 更多	积极	2022-06-01
				Enpatoran 100 mg BID	淵構壓觸襯膚餘願窪選(膚獵積壓選齋積餘蓋糧) = 積鑰淵選蓋襯憲製構廠獵選積鏇構選淵構鹽遞 (範鹹選遞製構顧廠鬱艱 ) 更多
NCT03676322 (Pubmed) 人工标引	临床1期	自身免疫性疾病	96	M5049 (single-dose)	繭鹽蓋糧積鏇壓遞餘糧(夢繭範築網襯遞蓋築積) = 膚艱鏇壓壓鹹鬱齋簾鹽壓製淵艱願鑰願膚醖範 (廠網製艱製鏇築範構鹹 ) 更多	积极	2021-10-01
				M5049 (multiple-dose)	繭鹽蓋糧積鏇壓遞餘糧(夢繭範築網襯遞蓋築積) = 鹽製憲鹹衊積築願願襯壓製淵艱願鑰願膚醖範 (廠網製艱製鏇築範構鹹 )