A Phase 1, Open-label Study to Investigate the Pharmacokinetics and Metabolism of GLPG3970 in Healthy Male Subjects Following a Single Oral Dose of GLPG3970 Relative to an Intravenous [14C]GLPG3970 Microtracer and Single Oral [14C]GLPG3970 Administration

A study in healthy male volunteers to assess how the radiolabelled test medicine is taken up and broken down by the body when given by short infusion into a vein and when given by the mouth in the form of a tablet and an oral solution.

开始日期2021-06-07

申办/合作机构

Galapagos NV

NCT04700280

/ Terminated临床2期

A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered GLPG3970 for 12 Weeks in Adult Subjects With Active Primary Sjögren's Syndrome

This is a first exploration of GLPG3970 in participants with active primary Sjogren's Syndrome (pSS) to evaluate the efficacy, safety and tolerability and to determine its pharmacokinetics (PK) profile compared to placebo.

开始日期2021-01-28

申办/合作机构

Galapagos NV

NCT04708184

/ Completed临床1期

A Randomized, Open-label, 3-period, Single-dose, Crossover Study in Healthy Adult Subjects to Assess the Relative Bioavailability of GLPG3970 Given as an Oral Tablet Formulation Versus the Oral Solution Formulation of GLPG3970 and to Assess the Effect of Food on the Oral Tablet Formulation.

This is a study to assess the relative bioavailability of a GLPG3970 oral tablet formulation compared to an oral solution formulation and the effect of food on the bioavailability of a single dose of the oral tablet formulation of GLPG3970. It will also evaluate the safety and tolerability of a single dose of GLPG3970.

开始日期2021-01-11

申办/合作机构

Galapagos NV

100 项与 GLPG-3970 相关的临床结果

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100 项与 GLPG-3970 相关的转化医学

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100 项与 GLPG-3970 相关的专利（医药）

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项与 GLPG-3970 相关的文献（医药）

2025-02-01·CLINICAL PHARMACOLOGY & THERAPEUTICS

Effects of GLPG3970 on Sulfasalazine and Methotrexate Pharmacokinetics in Healthy Adults: Two Open‐Label, Phase I, Drug–Drug Interaction Studies

Article

作者: Gistelinck, Fien ; Bellaire, Susan ; Dao, Justine ; Zabela, Volha ; van der Plas, Mariska

GLPG3970 is a selective salt‐inducible kinase 2/3 inhibitor intended for the treatment of inflammatory diseases. In vitro studies suggest GLPG3970 strongly inhibits breast cancer resistance protein (BCRP), indicating a possible interaction with BCRP substrates such as sulfasalazine (SSZ; a probe substrate for intestinal BCRP inhibition) and methotrexate (MTX), both inflammatory disease medications. Two open‐label, nonrandomized, phase I, drug–drug interaction (DDI) studies assessed the pharmacokinetics of SSZ 1,000 mg (NCT04720183) and MTX 7.5 mg (EudraCT: 2020‐000391‐37) with and without GLPG3970 350 mg. Healthy participants aged 18–55 years with wild‐type homozygous BCRP genotype (c421C/C) received: SSZ on day (D)1, GLPG3970 + SSZ on D5, and GLPG3970 2 hours after SSZ on D9 (N = 8; SSZ/GLPG3970 DDI study); MTX on D1, GLPG3970 + MTX on D5, and GLPG3970 on D6–8 (N = 15; MTX/GLPG3970 DDI study). Primary end points were AUC and Cmax (“exposure”) of SSZ and its metabolite (sulfapyridine [SPD]), SPD:SSZ AUC ratio (SSZ/GLPG3970 study), and AUC and Cmax (“exposure”) of MTX (MTX/GLPG3970 study). DDIs were evaluated using the geometric mean ratio of each end point; a > 2‐fold increase in SSZ or MTX exposure was deemed clinically relevant. GLPG3970 demonstrated mild inhibition of intestinal BCRP in vivo: GLPG3970 + SSZ increased SSZ exposure ~1.7–1.8‐fold and decreased SPD:SSZ ratio ~ 2‐fold vs. SSZ alone. GLPG3970 administered 2 hours after SSZ did not change the magnitude of the interaction. GLPG3970 + MTX had no relevant effect on MTX pharmacokinetics vs. MTX alone. Therefore, the strong in vitro BCRP inhibition was not confirmed in vivo. No safety concerns were observed when GLPG3970 was coadministered with SSZ or MTX.

2024-04-11·Journal of medicinal chemistry1区 · 医学

Discovery of Clinical Candidate GLPG3970: A Potent and Selective Dual SIK2/SIK3 Inhibitor for the Treatment of Autoimmune and Inflammatory Diseases

1区 · 医学

Article

作者: López-Ramos, Miriam ; Dupont, Sonia ; Amantini, David ; Jary, Hélène ; Merciris, Didier ; Joncour, Agnes ; Pereira Fernandes, Anna ; Desroy, Nicolas ; Roca Magadan, Carlos ; Tirera, Amynata ; Andrews, Martin ; Bucher, Denis ; De Vos, Steve ; Dos Santos, Aurélie ; Lavazais, Stephanie ; Temal-Laib, Taouès ; Drennan, Michael ; Monjardet, Alain ; Delachaume, Carole ; Jimenez, Juan-Miguel ; Borgonovi, Monica ; Wakselman, Emanuelle ; Laenen, Wendy ; Brys, Reginald ; Peixoto, Christophe ; Saccomani, Corinne

The salt-inducible kinases (SIKs) SIK1, SIK2, and SIK3 belong to the adenosine monophosphate-activated protein kinase (AMPK) family of serine/threonine kinases. SIK inhibition represents a new therapeutic approach modulating pro-inflammatory and immunoregulatory pathways that holds potential for the treatment of inflammatory diseases. Here, we describe the identification of GLPG3970 (32), a first-in-class dual SIK2/SIK3 inhibitor with selectivity against SIK1 (IC₅₀ of 282.8 nM on SIK1, 7.8 nM on SIK2 and 3.8 nM on SIK3). We outline efforts made to increase selectivity against SIK1 and improve CYP time-dependent inhibition properties through the structure-activity relationship. The dual activity of 32 in modulating the pro-inflammatory cytokine TNFα and the immunoregulatory cytokine IL-10 is demonstrated in vitro in human primary myeloid cells and human whole blood, and in vivo in mice stimulated with lipopolysaccharide. Compound 32 shows dose-dependent activity in disease-relevant mouse pharmacological models.

项与 GLPG-3970 相关的新闻（医药）

2023-02-24

·Endpoints

Galapagos goes 0-for-3 on inflammation program as it cuts an early-stage candidate

Galapagos has cut anti-inflammatory drug candidate GLPG4399 following the completion of an early-stage healthy volunteer trial, according to its 2022 annual report released Thursday afternoon. GLPG4399 was a SIK3 inhibitor, one in a line of such salt-inducible kinase (SIK) inhibitors that Galapagos has been trying to develop for inflammatory diseases like rheumatoid arthritis and ulcerative colitis. Originally, the biotech had been planning to move the drug forward in a study with rheumatoid arthritis patients in the middle of this year, but now it’s halting the program and going back to search for new SIK inhibitors. “Medicinal chemistry activities to identify SIK inhibitors with improved pharmacology continues,” Galapagos noted briefly in its press release. GLPG4399 was the third SIK inhibitor Galapagos brought out of the clinic — all part of a franchise Galapagos dubbed Toledo. The first candidate, GLPG3312, similarly only made it through healthy volunteer studies before Galapagos scrapped it. The second, GLPG3970, disappointed in Phase II trials in ulcerative colitis and rheumatoid arthritis, and though it showed some signs of efficacy in psoriasis, Galapagos opted to toss that candidate as well. The small pipeline prune comes after Galapagos laid off 200 staffers and discontinued work on its fibrosis and kidney disease programs, cuts that followed a long string of setbacks at the biotech. In December, Galapagos also announced that its chief business officer André Hoekema and chief medical officer Walid Abi-Saab are retiring, though the latter is remaining with the company until the end of May. Galapagos shares $GLPG fell almost 8% after the markets opened Friday. The biotech did not immediately return request for comment.

临床2期临床失败

2022-07-26

·PRNewswire

New Therapeutics Options in Rheumatoid Arthritis Pipeline as 120+ Key Companies are Working on Drug Profiles | DelveInsight

Rise in prevalence of rheumatoid arthritis, increase in demand for rheumatoid arthritis drugs, the entry of biosimilar drugs, the surge in geriatric population are the key factors driving the development of potential treatment of Rheumatoid arthritis. Major key players include Taisho Pharmaceutical, Zhejiang Hisun Pharmaceutical, SinoMab, Jiangsu Hengrui Medicine, RemeGen, GlaxoSmithKline, Modern Biosciences, Jiangsu Alphamab Biopharmaceuticals, and others. LAS VEGAS, July 26, 2022 /PRNewswire/ -- DelveInsight's ' Rheumatoid Arthritis Pipeline Insight 2022 ' report provides comprehensive global coverage of available, marketed, and pipeline rheumatoid arthritis therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the rheumatoid arthritis pipeline domain. Key Takeaways from the Rheumatoid Arthritis Pipeline Report DelveInsight's rheumatoid arthritis pipeline report depicts a robust space with 120+ active players working to develop 120 + pipeline therapies for rheumatoid arthritis treatment. Key rheumatoid arthritis companies such as Taisho Pharmaceutical, Zhejiang Hisun Pharmaceutical, SinoMab, Jiangsu Hengrui Medicine, RemeGen, GlaxoSmithKline, Modern Biosciences, Jiangsu Alphamab Biopharmaceuticals, Akros Pharma, Hanlim Pharm, Galapagos NV, Chong Kun Dang Pharmaceutical, Bristol Myers Squibb, AstraZeneca, Aclaris Therapeutics, Abivax, AbbVie, Synact Pharma, Gilead sciences, Mesoblast, Rottapharm Biotech, Eli Lilly and Company, Kiniksa Pharmaceuticals, Abcentra, Cyxone, Yungjin Pharm. Co., Ltd. Taiho Pharmaceutical, Oscotec Inc., Pfizer, Janssen Research & Development, Cipher Pharmaceuticals Inc., KLUS Pharma Inc., Revolo Biotherapeutics, Lynk Pharmaceuticals, Beijing Baylx Biotech, Hope Biosciences, Kangstem Biotech, Celltex Therapeutics, I-Mab Biopharma Co. Ltd., Synermore Biologics Co., Ltd, Oryn Therapeutics, Arthrogen, Bayer, Amgen, Draconis Pharma, Biozeus, Landos Biopharma, Imcyse, Kymera Therapeutics, RedHill Biopharma, 4D Pharma, CV6 Therapeutics, VYNE Therapeutics, MyMD Pharmaceuticals, Brickell Biotech Inc, Worg Pharmaceuticals, Almirall, Standigm, Metrion Biosciences, Jnana Therapeutics, Silo Pharma, SFA Therapeutics, Neutrolis Therapeutics, Ahead Therapeutics, Fresenius Kabi, Kidswell Bio, BioXpress Therapeutics, CinnaGen, Alvotech, Hetero Biopharma, Shanghai Henlius Biotech, Cadila Pharmaceuticals, Innovent Biologics, Torrent Pharmaceuticals, Emcure Pharmaceuticals, mAbxience, Shanghai Junshi Biosciences, Enosi Therapeutics, and others are evaluating novel rheumatoid arthritis treatment drugs candidate to improve the treatment landscape. Promising rheumatoid arthritis pipeline therapies in various stages of development includes TS152, HS-016, SM03, SHR0302, RC18, Otilimab, NI-0101, MBS2320, KN019, JTE-051, Interleukin 2, HL237, GLPG3970, Elsubrutinib, CKD-506, Branebrutinib, AZD9567, ATI-450, ABX464, ABBV 3373, ABBV 154, AP1189, F8IL10, AMT-101, GS-9876, CR 6086, LY 3462817, KPL-404, Orticumab, Rabeximod, YRA 1909, VIB4920, Varicella Zoster Vaccine, TAS5315, SKI-O-703, SAN-300, PF-06650833, Nipocalimab, CF-101, A223, IRL 201805, LNK 01001, PRTX-100, hUC-MSC infusion, HB-adMSC, LABP-104, VAY736, TJ003234 , SYN060, GS-5718, PF-06835375, Nivolumab, MH004, ORTD-1, ART-I02, FB704A, Amilo 5MER, CKD-374 , CFZ-533, BAY 1830839, AMG 570, JNJ-4703, CT-P47, BZ068, Invossa, LABP-69, ICM-203-R, NX-5948, KT-474 , Clarithromycin/clofazimine/rifabutin (RHB-104), Research programme: small molecule TYK2 inhibitors, MRx0006, CV6 1271, VYN201, MYMD-1, BBI 02, Research Programme: Immune mediated diseases, Foralumab, SPU-21, SFA002, NTR-441, Research programme: autoimmune disease therapeutics, AT_1001, MSB11456, MabionCD20, DMB-3113, GB232, GBS 005, TX17, BX 2922, Cinnora, AVT02, MYL-1401A, and others. In July 2022, Enosi Therapeutics, announced a partnership with Danuo Science Group, based in Hong Kong, to further develop two products currently in Enosi's pipeline for Greater China. Enosi's Growth Factor Trap (EN-2000 Program) and TNFR1 Blocker (EN-1000 Program) were licensed as part of the partnership. Both programs have the potential to be used as cross-over drugs to treat cancer and autoimmune diseases. EN-2000 blocks inflammatory growth factors that drive cancer and rheumatoid arthritis while EN-1000 is a specific blocker of TNFR1, which Enosi believes may be useful in treating autoimmune disease. In February 2022, Biogen Inc. and Xbrane Biopharma AB announced that they have entered into a commercialization and license agreement to develop, manufacture, and commercialize Xcimzane™, a preclinical monoclonal antibody that is a proposed biosimilar referencing CIMZIA® (certolizumab pegol). In June 2022, Biogen Inc. and Bio-Thera Solutions, Ltd. presented positive Phase III data for BIIB800 (BAT1806), a biosimilar candidate referencing. The double-blind 52-week Phase III study randomized 621 patients with moderate to severe rheumatoid arthritis to receive either BIIB800 or the reference tocilizumab administered intravenously every 4 weeks at a dose of 8 mg/kg for the first 24 weeks. Data from the Phase III comparative clinical trial demonstrated that the investigational biosimilar candidate BIIB800 has equivalent efficacy and comparable safety and immunogenicity profile to the reference tocilizumab product. In June 2022, Revolo Biotherapeutics announced that it was awarded an Innovative Medicines Designation, or Innovation Passport, from the Medicines and Healthcare products Regulatory Agency (MHRA) for its immune-resetting drug candidate, '1805, for the treatment of patients with moderately to severely active Rheumatoid Arthritis (RA). In February 2022, Revolo Biotherapeutics secured approval from the UK Medicines and Healthcare products Regulatory Agency (MHRA) to initiate two Phase II trials of its autoimmune disease drug candidate '1805. One of the trials will enrol moderate-to-severe active rheumatoid arthritis (RA) patients while another Phase II trial will have individuals with non-infectious, active, intermediate, or posterior uveitis or panuveitis. In December 2021, Theramex, entered into an agreement with Enzene Biosciences Limited to develop, register, and commercialize a biosimilar drug of Roche's reference medicine RoActemra (Tocilizumab). Tocilizumab, in combination with Methotrexate (MTX), is indicated for the treatment of rheumatoid arthritis. It is planned to be commercialized from 2026 in Europe, the UK, Switzerland, and Australia. Obefazimod is an oral, first-in-class, small molecule being developed by Abivax in Phase II stage of development. Obefazimod generated promising pre-clinical data from collagen-induced arthritis animal models that were the basis for moving into the Phase IIa clinical trial in rheumatoid arthritis (RA). Zunsemetinib, an Investigational Oral MK2 Inhibitor, is being developed by Aclaris Therapeutics. Aclaris initiated study activities and began activating sites in December 2021 in the following two studies: ATI-450-RA-202: Phase IIb clinical trial of zunsemetinib in subjects with moderate to severe rheumatoid arthritis (RA). This is Aclaris' second Phase II clinical trial of zunsemetinib in subjects with moderate to severe RA and is primarily designed to assess the efficacy of multiple doses of zunsemetinib to aid in the selection of an optimal dose to progress in future development. Request a sample and discover the recent advances in rheumatoid arthritis treatment @ Rheumatoid Arthritis Pipeline Outlook The rheumatoid arthritis pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage rheumatoid arthritis products, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the rheumatoid arthritis pipeline landscape. Rheumatoid Arthritis Overview Rheumatoid arthritis is classified as an autoimmune disorder. It occurs when the immune system, which is supposed to defend, malfunctions and begins to attack our own tissues. It causes inflammation in the lining of the joints (the synovium). As a result, joints may become red, warm, swollen, and painful, which are common rheumatoid arthritis symptoms. The exact rheumatoid arthritis causes are still unknown. Rheumatoid arthritis can be difficult to detect in its early stages since the early signs and symptoms are similar to those of many other diseases. There is no single blood test or physical finding that can validate the rheumatoid arthritis diagnosis. Rheumatoid arthritis has no known cure. However, rheumatoid arthritis clinical trials show that remission of symptoms is more frequent when rheumatoid arthritis treatment with disease-modifying antirheumatic medicines started early (DMARDs). Find out more about rheumatoid arthritis treatment @ Rheumatoid Arthritis Treatment Drugs A snapshot of the Rheumatoid Arthritis Pipeline Drugs mentioned in the report: Learn more about the novel and emerging rheumatoid arthritis pipeline therapies @ Rheumatoid Arthritis Clinical Trials Rheumatoid Arthritis Therapeutics Assessment The rheumatoid arthritis pipeline report proffers an integral view of rheumatoid arthritis emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Rheumatoid Arthritis Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intra-ocular, Intra-articular, Intrathecal, Intravenous, Oral, Parenteral, Ophthalmic, Subcutaneous, Topical, Transdermal Therapeutics Assessment By Molecule Type: Oligonucleotide, Peptide, Small molecule Therapeutics Assessment By Mechanism of Action: Interleukin 6 inhibitor, Tumour necrosis factor-alpha inhibitor, CD22 antigen inhibitor, Janus kinase 1 inhibitor, B cell activating factor inhibitor, Granulocyte-macrophage colony-stimulating factor antagonist, Toll-like receptor 4 antagonist, Emt protein-tyrosine kinase inhibitor, Fibroblast growth factor modulators; T lymphocyte inhibitors, Bacteria replacements. Key Rheumatoid Arthritis Companies: Taisho Pharmaceutical, Zhejiang Hisun Pharmaceutical, SinoMab, Jiangsu Hengrui Medicine, RemeGen, GlaxoSmithKline, Modern Biosciences, Jiangsu Alphamab Biopharmaceuticals, Akros Pharma, Hanlim Pharm, Galapagos NV, Chong Kun Dang Pharmaceutical, Bristol Myers Squibb, AstraZeneca, Aclaris Therapeutics, Abivax, AbbVie, Synact Pharma, Gilead sciences, Mesoblast, Rottapharm Biotech, Eli Lilly and Company, Kiniksa Pharmaceuticals, Abcentra, Cyxone, Yungjin Pharm. Co., Ltd. Taiho Pharmaceutical, Oscotec Inc., Pfizer, Janssen Research & Development, Cipher Pharmaceuticals Inc., KLUS Pharma Inc., Revolo Biotherapeutics, Lynk Pharmaceuticals, Beijing Baylx Biotech, Hope Biosciences, Kangstem Biotech, Celltex Therapeutics, I-Mab Biopharma Co. Ltd., Synermore Biologics Co., Ltd, Oryn Therapeutics, Arthrogen, Amgen, Biozeus, Landos Biopharma, Imcyse, Kymera Therapeutics, RedHill Biopharma, 4D Pharma, CV6 Therapeutics, VYNE Therapeutics, MyMD Pharmaceuticals, Brickell Biotech Inc, Worg Pharmaceuticals, Almirall, Standigm, Metrion Biosciences, Jnana Therapeutics, Silo Pharma, SFA Therapeutics, Neutrolis Therapeutics, Ahead Therapeutics, Fresenius Kabi, Kidswell Bio, BioXpress Therapeutics, CinnaGen, Alvotech, Hetero Biopharma, Shanghai Henlius Biotech, Cadila Pharmaceuticals, Innovent Biologics, Torrent Pharmaceuticals, Emcure Pharmaceuticals, mAbxience, Shanghai Junshi Biosciences, Enosi Therapeutics, and others Key Rheumatoid Arthritis Pipeline Therapies: TS152, HS-016, SM03, SHR0302, RC18, Otilimab, NI-0101, MBS2320, KN019, JTE-051, Interleukin 2, HL237, GLPG3970, Elsubrutinib, CKD-506, Branebrutinib, AZD9567, ATI-450, ABX464, ABBV 3373, ABBV 154, AP1189, F8IL10, AMT-101, GS-9876, CR 6086, LY 3462817, KPL-404, Orticumab, Rabeximod, YRA 1909, VIB4920, Varicella Zoster Vaccine, TAS5315, SKI-O-703, SAN-300, PF-06650833, Nipocalimab, CF-101, A223, IRL 201805, LNK 01001, PRTX-100, hUC-MSC infusion, HB-adMSC, LABP-104, VAY736, TJ003234 , SYN060, GS-5718, PF-06835375, Nivolumab, MH004, ORTD-1, ART-I02, FB704A, Amilo 5MER, CKD-374 , CFZ-533, BAY 1830839, AMG 570, JNJ-4703, CT-P47, BZ068, Invossa, LABP-69, ICM-203-R, NX-5948, KT-474 , Clarithromycin/clofazimine/rifabutin (RHB-104), Research programme: small molecule TYK2 inhibitors, MRx0006, CV6 1271, VYN201, MYMD-1, BBI 02, Research Programme: Immune mediated diseases, Foralumab, SPU-21, SFA002, NTR-441, Research programme: autoimmune disease therapeutics, AT_1001, MSB11456, MabionCD20, DMB-3113, GB232, GBS 005, TX17, BX 2922, Cinnora, AVT02, MYL-1401A, and others. Dive deep into rich insights for drugs for rheumatoid arthritis, visit @ Rheumatoid Arthritis Medications Table of Contents For further information on the rheumatoid arthritis pipeline therapeutics, reach out @ Drugs for Rheumatoid Arthritis Related Reports Rheumatoid Arthritis Market Rheumatoid Arthritis Market Insights, Epidemiology, and Market Forecast-2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key rheumatoid arthritis companies including Abivax, UCB, Sierra Oncology, Taisho, among others. Rheumatoid Arthritis Epidemiology Forecast Rheumatoid Arthritis Epidemiology Forecast to 2032 report delivers an in-depth understanding of the disease, historical and forecasted rheumatoid arthritis epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Juvenile Rheumatoid Arthritis Pipeline Juvenile Rheumatoid Arthritis Pipeline Insight, 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products and the key juvenile rheumatoid arthritis companies, including Novartis, AbbVie, Eli Lilly and Company, Sanofi, among others. Juvenile Rheumatoid Arthritis Market Juvenile Rheumatoid Arthritis Market Insights, Epidemiology, and Market Forecast-2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key juvenile rheumatoid arthritis companies including Novartis, AbbVie, Eli Lilly and Company, Sanofi, among others. Psoriatic Arthritis Pipeline Psoriatic Arthritis Pipeline Insight, 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key psoriatic arthritis companies, including Mylan, Celltrion, Pfizer, Amgen, among others. Psoriatic Arthritis Market Psoriatic Arthritis Market Insights, Epidemiology, and Market Forecast-2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key psoriatic arthritis companies including Mylan, Celltrion, Pfizer, Amgen, among others. Other Trending Reports Persistent Depressive Disorder Market | Gene Therapy for Ocular Rare Disease Market | Congestive Heart Failure Market | CRISPR Therapies Pipeline | Desmoplastic Small Round Cell Tumors Market | India Healthcare Outlook Report | Psychosis Market | Dental Lasers Market | Primary Immune Deficiency Market I Dyslipidemia Market | Lateral Epicondylitis Disease Market | Castration-Resistant Prostate Cancer Market | Metrorrhagia Market | Global Messenger RNA-based Vaccines and Therapeutics Market | Negative Pressure Wound Therapy Systems Market | US Healthcare Outlook Report | Mucinous Cystic Neoplasms Market | Hot Flashes Market | Varicose Veins - Market | Hemostats Market | Injectable Drug Delivery Devices Market | Breast Pumps Market | Physiotherapy Equipment Market | Trastuzumab Biosimilars Insight | Deep Brain Stimulation Devices Market | Retinoblastoma Market | Venous Stenosis Market | Tumor Ablation Market | Substance Abuse Market | Insulin Glargine Biosimilar Insight | Interspinous Spacers Market | Anti-hypertension Market Latest Healthcare Blogs Knee Osteoarthritis Pipeline Rheumatoid Arthritis Market Scenario Juveline Idiopathic Arthritis Therapy Market About DelveInsight DelveInsight is a leading Business Consultant, and Market Research firm focused exclusively on life sciences. Connect with us at LinkedIn Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

2022-03-16

·E药经理人

O药终止两项临床，GSK与默克分道扬镳，吉利德50亿美元合作太失败？MNC数十亿美元合作背后的逻辑是什么？

从BMS到默沙东与阿斯利康，全球制药巨头们近来似乎陷入了从甜蜜合作到分道扬镳的“临床研发失败”怪圈。 01、1+1未必大于2 与BMS达成36亿美元合作的Nektar公司，近来遭遇两项临床研究失败。 3月14日，BMS和Nektar共同宣布了III期临床试验PIVOT IO-001研究的首次分析结果。该项研究评估了偏向性IL-2 bempegaldesleukin联合PD-1单抗纳武利尤单抗（Opdivo）一线治疗不可切除或转移性黑色素瘤的疗效，独立数据监测委员会（DMC）的分析结果显示，双药治疗组未能显示出相较于单药组的临床获益。据悉，基于该研究未能达到无进展生存期（PFS）和客观缓解率（ORR）主要终点，且第3个主要终点总生存期（OS）在第一次中期分析中也没有统计学意义上的改善，两家公司决定揭盲并不对研究终点进行额外分析。同时，BMS和Nektar还将终止招募并揭盲正在进行中的联合疗法用于黑色素瘤辅助治疗的PIVOT-12研究，这两项研究中的患者将被告知他们在试验中所接受的治疗方式，并和医师商议后决定后续治疗方案的调整。自2018年官宣总额高达36亿美元的全球开发战略以来，BMS与Nektar在开发联合癌症疗法的合作不断深入，尤其是Nektar的长效IL-2免疫刺激疗法bempegaldesleukin（NKTR-214）与Opdivo的联合应用，曾被FDA授予突破性疗法认定，治疗初治无法切除或转移性黑色素瘤患者。此外，NKTR-214还获得FDA授予的孤儿药资格，用于治疗IIb至IV期黑色素瘤。虽然两项针对治疗黑色素瘤的临床相继终止，但bempegaldesleukin与Opdivo的联合治疗仍有针对肌层浸润性膀胱癌、肾细胞癌、头颈部鳞状细胞癌等另外四项研究正在展开，其中关于肾细胞癌和尿路上皮癌的两项临床试验的初步研究结果定于今年上半年公布。作为免疫疗法的两大“扛把子”，BMS宣布O药联合疗法遭遇临床试验失败的次日，默沙东宣布终止K药一项联合疗法的临床试验。昨日，默沙东宣布其重磅炸弹Keytruda与阿斯利康的PARP抑制剂Lynparza的联合疗法在先前治疗过的转移性去势抵抗性前列腺癌（mCRPC）患者中并未能优于目前临床常用的抗雄激素疗法，决定终止Keytruda-Lynparza组合疗法的研发。试验结果显示，与强生Zytiga或辉瑞Xtandi相比，Keytruda-Lynparza联合疗法未能进一步延长mCRPC患者的生命，也没能阻止肿瘤进展。值得注意的是，作为全球最畅销的PD-1与最畅销的PARP抑制剂，K药与Lynparza均是各自治疗领域内的佼佼者。但两个重磅炸弹产品的联用，却未能取得1+1＞2的效果。甚至，更糟糕的情况是，Keytruda-Lynparza联合疗法还导致了mCRPC患者3-5级药物相关严重副作用的发生率增长。在此次III期Keylynk-010试验的中期分析结果遭遇了惨败后，默沙东决定遵循独立数据监测委员会的建议，尽早停止组合疗法的研发试验。 02、九死一生而不悔如果梳理全球制药巨头如今的研发管线不难发现，通过收购、投资、授权合作等模式，实现对自身新药研发管线的拓宽，是大药企加速药物研发脚步过程中普遍会选择的战略。一方面，对已上市药物而言，通过联用寻求扩大适应证范围、提高单药治疗效果的机会；另一方面，大药企也在积极寻找那些尚处于临床阶段但展示出优于现有治疗方案的临床试验数据的药物，通过项目授权引入或收购、投资公司的方式将它们纳入自身的研发体系，培养成为下一个业绩增长点。虽然这种外部合作能够快速补充自身管线，但大药企前期动辄数亿美元甚至数十亿美元巨额资金投入换来的项目，面临着临床试验失败、市场竞争格局变化、项目研发重心调整而终止合作与研发的“竹篮打水一场空”般的不确定性。正如50亿美元合作却几乎全部打水漂的吉利德，与Galapagos达成的为期10年合作几乎被看作近年来最失败的交易之一。 2019年07月，吉利德与Galapagos宣布签署一项为期10年的全球研发合作协议。吉利德通过支付一笔39.5亿美元的预付款和一笔11亿美元的股权投资，获得Galapagos一个创新的化合物组合，包括目前正在进行临床试验的6个分子、20多个临床前项目以及一个经验证的药物发现平台。合作的开始往往是前途光明且充满信心的。促成吉利德达成这项合作的原因是多重的。早在2015年，吉利德就与Galapagos曾达成总额高达20亿美元的协议，共同开发由Galapagos发现的Filgotinib。Filgotinib是一种高度选择性JAK1抑制剂，用于治疗中度至重度活动性类风湿性关节炎成人患者。彼时Filgotinib表现出的优异的临床数据让吉利德对Filgotinib信心十足，甚至在2019年花费8000万美元从Ultragenyx公司购买了优先审评券（PRV）来加速FDA的审查。不只是Filgotinib，Galapagos还拥有两款FIC级别的化合物——GLPG1690和GLPG1972。GLPG1690临床用于特发性肺纤维化的治疗，资料显示，在IIa期临床试验中展现出优于现有治疗方案的表现；GLPG1972临床开发用于骨关节炎的治疗，在早期的临床1b试验获得了积极的初步顶线研究数据。这也就不难解释吉利德为何希望与Galapagos达成紧密合作。但面对九死一生的新药研发，一切都是未知的。进入2020年，吉利德与Galapagos的合作就像进入了水逆期。先是花费8000万美元购买优先审评券以加速审批的JAK抑制剂Filgotinib遭美国FDA拒绝批准，虽然目前双方还在欧洲和日本市场开展Filgotinib的销售合作，但错失美国市场，对吉利德来讲，损失是巨大的。同年10月，GLPG1972的II期ROCCELLA试验的主要结果未能达到预期，宣告其在骨关节炎领域的研究失败。临床研究的失败对双方的打击延续到了2021年。另一个合作药物GLPG1690在特发性肺纤维化（IPF）患者中的III期ISABELA试验也遭遇终止。独立数据监测委员会认为，GLPG1690的获利-风险状况不再值得进一步开发。同时，双方也停止了关于GLPG1690的所有临床试验，包括在弥漫性皮肤系统性硬化症中的IIa期NOVESA研究的长期拓展。这也被看作可能是出现了“安全性问题”。双方的另一款候选药物SIK2/3抑制剂GLPG3970在类风湿性关节炎/溃疡性结肠炎领域的临床试验的失败更是被列入Fiercebiotech发布的2021年十大临床失败案例榜单之中。虽然目前双方的合作还在进行中，但围绕合作药物的安全性隐患与市场竞争格局变化带来的压力来看，两家公司计划的长达10年的合作可能提前终止。其实，因为临床数据不佳、市场格局变化、安全性隐患等问题造成的合作终止并不少见。仅2021年，罗氏、默沙东、GSK、强生等众多MNC都因临床试验数据不佳而选择终止了与各自项目合作方的交易。罗氏与Atea终止关于口服新冠药物AT-527的合作是过去一年间首付款金额最高的终止合作的交易，2020年10月22日，Atea与罗氏达成合作，授予罗氏在美国境外地区研究、开发和商业化AT-527的权益，同时获得3.5亿美元的预付款、未来的里程碑付款和专利使用费。一年后的2021年11月17日，Atea宣布终止与罗氏联合开发新冠口服药物AT-527的项目，合作终止的原因可能与AT-527 II期临床结果不佳相关。 GSK与默克关于结合抗PD-L1和TGF-β抑制的双功能融合蛋白Bintrafusp alfa研发的失败，也让业界感到遗憾。Bintrafusp alfa过去优异的临床数据让这一疗法被宣传为Keytruda未来强有力的竞争对手，但是Bintrafusp alfa在过去一年内遭遇四项II/III期临床研究失败，让GSK与默克不得不终止研发。这项首付款达3亿欧元、总交易金额37亿欧元的强强联合也就此作罢。Bintrafusp alfa研发项目的终止，更让众多“跟进者”重新审视起PD-L1/TGF-β双抗临床研究的价值。有数据显示，当前全球排名前十的跨国药企中，60%~70%的产品都是通过对外合作进入管线的。有国内药企负责人曾对E药经理人表示，虽然面临巨大的研发风险，但寻找新的重磅药物与业绩增长的新动力关乎着大药企的生存与发展。授权合作作为当前最为流行的创新模式，大药厂通过“买买买”的授权交易能够快速补充管线甚至掌握一些疾病领域、新靶点研究的先机。内容来源于网络，如有侵权，请联系删除，谢谢。

合作免疫疗法抗体并购突破性疗法

100 项与 GLPG-3970 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
原发性干燥综合征	临床2期	德国	Galapagos NV	2021-01-28
原发性干燥综合征	临床2期	希腊	Galapagos NV	2021-01-28
原发性干燥综合征	临床2期	匈牙利	Galapagos NV	2021-01-28
原发性干燥综合征	临床2期	波兰	Galapagos NV	2021-01-28
原发性干燥综合征	临床2期	乌克兰	Galapagos NV	2021-01-28
类风湿关节炎	临床2期	美国	Galapagos NV	2020-10-12
类风湿关节炎	临床2期	保加利亚	Galapagos NV	2020-10-12
溃疡性结肠炎	临床2期	美国	Galapagos NV	2020-10-05
溃疡性结肠炎	临床2期	摩尔多瓦	Galapagos NV	2020-10-05
溃疡性结肠炎	临床2期	波兰	Galapagos NV	2020-10-05

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临床结果

适应症

分期

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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


NCT04700280 (GLIDER, CTgov)	临床2期	原发性干燥综合征	31	GLPG3970 (GLPG3970)	顧願網憲觸獵顧糧襯積(積窪選膚廠選壓網夢構) = 蓋衊鹹鏇鏇製簾餘窪鑰壓鏇鏇窪艱糧鏇鏇鹽窪 (醖築觸蓋壓窪繭網製壓, 1.56) 更多	-	2023-09-18
				Placebo (Placebo)	顧願網憲觸獵顧糧襯積(積窪選膚廠選壓網夢構) = 窪構簾鹽壓衊淵壓鑰網壓鏇鏇窪艱糧鏇鏇鹽窪 (醖築觸蓋壓窪繭網製壓, 2.03) 更多
NCT04577794 (SEA TURTLE, CTgov)	临床2期	溃疡性结肠炎	31	GLPG3970 (GLPG3970)	範遞鬱鏇鹹鹽網繭獵襯(鏇鏇憲鏇窪鹹膚衊糧艱) = 鏇積簾範壓繭鏇範鏇積築網衊鹹膚鬱衊糧夢網 (選顧觸憲製鹽鹹遞鏇積, 0.57) 更多	-	2023-01-27
				Placebo (Placebo)	範遞鬱鏇鹹鹽網繭獵襯(鏇鏇憲鏇窪鹹膚衊糧艱) = 蓋製夢鹽艱糧構鑰選觸築網衊鹹膚鬱衊糧夢網 (選顧觸憲製鹽鹹遞鏇積, 0.85) 更多
NCT04577781 (LADYBUG, CTgov)	临床2期	类风湿关节炎	28	GLPG3970 (GLPG3970)	醖膚餘觸襯鏇顧構鹽鹽(壓鬱艱憲繭積衊願鹽夢) = 憲醖廠蓋鏇簾夢製醖鏇壓積鬱艱壓範齋蓋憲鏇 (簾醖窪淵衊範憲窪鏇網, 0.224) 更多	-	2022-07-18
				Placebo (Placebo)	醖膚餘觸襯鏇顧構鹽鹽(壓鬱艱憲繭積衊願鹽夢) = 鬱憲壓淵鬱網膚憲廠壓壓積鬱艱壓範齋蓋憲鏇 (簾醖窪淵衊範憲窪鏇網, 0.258) 更多
NCT04106297 (CALOSOMA, NEWS) 人工标引	临床1期	炎症	26	GLPG-3970	齋鬱膚製簾願遞積鑰範(鏇範鹹膚築蓋蓋願憲鹽) = 艱鏇鹽醖鹹積鑰製鑰築鬱簾糧鬱鬱壓鏇壓廠膚 (膚襯鬱鬱醖衊鑰衊選網 )	积极	2021-07-14
				Placebo	齋鬱膚製簾願遞積鑰範(鏇範鹹膚築蓋蓋願憲鹽) = 繭築鏇艱衊膚顧網鏇範鬱簾糧鬱鬱壓鏇壓廠膚 (膚襯鬱鬱醖衊鑰衊選網 )
NCT04577794 (SEA TURTLE, Corporate Publications) 人工标引	临床2期	活动性重度溃疡性结肠炎	31	GLPG-3970	鬱壓觸襯鹹遞鏇鏇窪製(範簾淵顧鬱鹽積製顧願) = 製範衊艱餘觸顧醖餘構鹹鹽網襯窪醖鏇顧鹽鏇 (膚網製醖糧鏇顧獵積鑰 ) 更多	不佳	2021-07-14
				Placebo	鬱壓觸襯鹹遞鏇鏇窪製(範簾淵顧鬱鹽積製顧願) = 壓獵糧顧鹽觸鹹觸選範鹹鹽網襯窪醖鏇顧鹽鏇 (膚網製醖糧鏇顧獵積鑰 ) 更多
NCT04577781 (GlobeNewswire) 人工标引	临床2期	炎症	28	GLPG-3970	鏇鹽壓願壓醖獵醖鹹積(遞範遞鏇糧觸鏇糧夢糧) = 鬱獵網艱鏇鹹鑰蓋鑰鬱範鏇網鹽壓觸鏇鏇淵鹽 (鹹構觸遞遞憲艱壓觸鬱 )	不佳	2021-07-14
				Placebo	鏇鹽壓願壓醖獵醖鹹積(遞範遞鏇糧觸鏇糧夢糧) = 築簾範膚範鬱蓋網艱齋範鏇網鹽壓觸鏇鏇淵鹽 (鹹構觸遞遞憲艱壓觸鬱 )