DOCSLIB.ORG

Effectiveness of Mavrilimumab in Viral Infections Including SARS-Cov-2 Infection - a Brief Review

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Effectiveness of Mavrilimumab in Viral Infections Including SARS-Cov-2 Infection - a Brief Review Infect Chemother. 2021 Mar;53(1):1-12 https://doi.org/10.3947/ic.2020.0109 pISSN 2093-2340·eISSN 2092-6448 Review article Effectiveness of Mavrilimumab in Viral Infections Including SARS-CoV-2 Infection - A Brief Review Kinal Bhatt 1, Radhika Garimella 2, Rahima Taugir 3, Isha Mehta 4, Muhammad Jamal 5, Rupalakshmi Vijayan 6, Rita Offor 7, Kanayo Nwankwo 8, Uroosa Arif 9, Khurram Waheed 10, Priyanka Kumari 11, Maulik Lathiya 12, George Michel 13, Naushira Pandya 14, John Halpern 14, Hassan Nasir 14, and Marcos A. Sanchez-Gonzalez 1 1Division of Clinical & Translational Research, Larkin Health System, South Miami, FL, USA 2Dr. NTR University of Health Sciences, Andhra Pradesh, India 3Medical University of the Americas, St. Kitts and Nevis 4Windsor University School of Medicine, St. Kitts and Nevis Received: Sep 15, 2020 5Beihua University, Jilin City, China Accepted: Feb 17, 2021 6Kasturba Medical College, Mangalore, India 7Texas A and M University, College Station, Texas, USA Corresponding Author: 8Ebonyi State University, Abakaliki, Nigeria Kinal Bhatt, MD, MPH 9Khyber Teaching Hospital, Peshawar, Pakistan Division of Clinical & Translational Research, 10Lady Willingdon Hospital, Lahore, Pakistan Larkin Health System, 7031 SW 62nd Ave South 11Chandka Medical College, Larkana, Pakistan Miami, FL 33124, USA. 12Jeevandip Hospital, Surat, India 13 Tel: (928) 225 0273 Department of Internal Medicine, Larkin Health System, South Miami, FL, USA 14 E-mail: [email protected] Larkin Health System, South Miami, FL, USA Copyright © 2021 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society ABSTRACT for AIDS This is an Open Access article distributed Hyperinflammation and cytokine storm has been noted as a poor prognostic factor in under the terms of the Creative Commons patients with severe pneumonia related to coronavirus disease 2019 (COVID-19). In Attribution Non-Commercial License (https:// COVID-19, pathogenic myeloid cell overactivation is found to be a vital mediator of damage creativecommons.org/licenses/by-nc/4.0/) to tissues, hypercoagulability, and the cytokine storm. These cytokines unselectively which permits unrestricted non-commercial use, distribution, and reproduction in any infiltrate various tissues, such as the lungs and heart, and nervous system. This cytokine medium, provided the original work is properly storm can hence cause multi-organ dysfunction and life-threatening complications. cited. Mavrilimumab is a monoclonal antibody (mAb) that may be helpful in some cases with COVID-19. During an inflammation, Granulocyte-macrophage colony-stimulating factor ORCID iDs Kinal Bhatt (GM-CSF) release is crucial to driving both innate and adaptive immune responses. The https://orcid.org/0000-0003-0261-9643 GM-CSF immune response is triggered when an antigen attaches to the host cell and induces Radhika Garimella the signaling pathway. Mavrilimumab antagonizes the action of GM-CSF and decreases https://orcid.org/0000-0002-0726-6923 the hyperinflammation associated with pneumonia in COVID-19, therefore strengthening Rahima Taugir the rationale that mavrilimumab when added to the standard protocol of treatment https://orcid.org/0000-0001-5769-6203 could improve the clinical outcomes in COVID-19 patients, specifically those patients Isha Mehta https://orcid.org/0000-0002-6628-1365 with pneumonia. With this review paper, we aim to demonstrate the inhibitory effect of Muhammad Jamal mavrilimumab on cytokine storms in patients with COVID-19 by reviewing published clinical https://orcid.org/0000-0003-2294-3299 trials and emphasize the importance of extensive future trials. Rupalakshmi Vijayan https://orcid.org/0000-0002-8419-3238 Keywords: COVID-19; SARS-CoV2; Mavrilimumab; Cytokine storm; Monoclonal antibody https://icjournal.org 1 Mavrilimumab in COVID-19 Rita Offor BACKGROUND https://orcid.org/0000-0002-1671-2008 Kanayo Nwankwo The Angiotensin Converting Enzyme-2 (ACE2) receptor enzyme is expressed is broadly https://orcid.org/0000-0002-4355-1991 expressed on the cell membranes of cells, an endogenous membrane protein that promotes Uroosa Arif https://orcid.org/0000-0003-3229-5790 COVID-19 infection with the extracellular peptidase domain enabling virus entry, using Khurram Waheed most prominent Spike glycoprotein (S), which is responsible for receptor attachment and https://orcid.org/0000-0002-0665-1061 allowing the virus to enter the host cell via membrane fusion. [1, 2]. Most of the lung damage Priyanka Kumari leading to respiratory failure needing mechanism ventilation is contributed to inflammatory https://orcid.org/0000-0002-6656-3637 cytokines [Interluekin-6, interferon-γ, and granulocyte-monocyte stimulating factor (GM- Maulik Lathiya https://orcid.org/0000-0002-3593-3850 CSF)]. GM-CSF is produced by many cells, including macrophages, T-cells, fibroblasts, George Michel endothelial cells, epithelial cells, and tumor cells; found to be increased in COVID-19 patients https://orcid.org/0000-0002-9899-8205 in comparison to healthy controls. Therefore, inhibition of GM-CSF or GM-CSF receptor Naushira Pandya is beneficial to reduce lung inflammation and therefore found to have a direct impact on https://orcid.org/0000-0001-9388-9504 improved oxygenation, reduced hospitalization, and mortality rate [3]. John Halpern https://orcid.org/0000-0002-1006-7220 Hassan Nasir COVID-19 intensive care unit (ICU) patients are found to have increased levels of several https://orcid.org/0000-0002-3544-1944 inflammatory cytokines: interleukin (IL)-2, IL-6, IL-7, ferritin, granulocyte-colony stimulating Marcos A. Sanchez-Gonzalez factor (G-CSF), granulocyte-monocyte stimulating factor (GM-CSF), interferon-γ-inducible https://orcid.org/0000-0002-7585-708X protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory Conflict of Interest protein 1-α (MIP1-α), and tumor necrosis factor-α (TNF-α) [3]. So far, increased IL-6 and No conflicts of interest. ferritin are associated with the worst prognostic factor in these patients. Researchers have discovered increased IL-1β and IL-6 are found along with increased ferritin. A phase 3 trial Author Contributions of IL-1 receptor antagonist, Anakinra, has shown a significant survival rate compared to a Conceptualization: KB, KW. Data curation: KB. Investigation: KB. Methodology: KB. placebo group [3]. As a myeloid cell growth factor and pro-inflammatory cytokine, GM- Project administration: KB, KW. Resources: CSF might be the most important factor in immunopathological sequelae of COVID-19. KB. Supervision: KB, GM, NP, JH, HN, MASG. GM-CSF is also an important agent that maintains pulmonary function and lung sentinel Validation: KB, MASG. Visualization: KB, MJ, cell-mediated immunity. Pulmonary GM-CSF stimulates PU.1 transcription factor in alveolar MASG. Writing - original draft: KB, RG, RT, IM, macrophage enabling their maturation and differentiation. This helps in the prevention MJ, RV, RO, KN, UA, PK, ML. Writing - review & of infection of alveolar macrophages by promoting virion clearance and destruction. editing: KB, IM, KW, MASG. Interruption of GM-CSF signaling can impair the GM-CSF receptor, and in turn, interrupt alveolar macrophage maturation, exposing to infections [4]. GM-CSF can also trigger the overexpression of IL-1, IL-6, TNF, and chemokines. A GM-CSF-targeted treatment strategy might have broader effects in restricting the overactive immunity than other immunomodulatory modalities [5]. MECHANISM OF ACTION OF MAVRILIMUMAB IN VIRAL INFECTIONS Mavrilimumab formerly known as (CAM-3001) is a human mAb (IgG4), inhibits granulocyte- macrophage colony-stimulating factor receptor alpha (GM-CSFR-α) and thus antagonizes GM-CSF signaling (Fig. 1) [6]. GM-CSFR is a heterodimer that consists of two subunits, alpha and beta chain. The alpha subunit is a binding site for GM-CSF and the beta chain is involved in signal transduction. The association of alpha and beta subunit results in receptor activation and downstream activation of multiple signaling pathways [7, 8]. GM-CSF, a hematopoietic growth factor that has a role in immunomodulation. GM-CSF when bind to its receptor, leads to an increase in the release of inflammatory cytokines from monocytes (macrophages) and polymorphonuclear leucocytes (neutrophils). The resulting activation of ERK1/2 (extracellular signal-regulated protein kinase) and NF-κB (Nuclear factor-κB) pathway leads to inflammatory https://icjournal.org https://doi.org/10.3947/ic.2020.0109 2 Mavrilimumab in COVID-19 SARS-CoV GM-CSF GM-CSF Mavrilimumab Cytokine Storm α β IL- IL- α β Beta Intracellular signalling Intracellular signalling GM-CSF Macrophage MMacrophage Intracellular Monocyte GM-CSF Pro-inflammatory signalling Dendritic cells cytokines Neutrophil (IL-, IL-, TNF, IL- ) Antigen Resting Activation Activated presenting T-cells T-cells cells GM-CSF Figure 1. The immunological response induced by an antigen upregulating GM-CSF in inflamed tissue [6]. SARS-CoV-2, severe acute respiratory syndrome Coronavirus 2; GM-CSF, granulocyte-macrophage colony-stimulating factor. response as well. GM-CSF signaling leads to activation of several other pathways such as recruitment and activation of Janus kinase 2 (JAK-2)-signal transducer and activator of transcription 5 (STAT-5), mitogen-activated protein kinase (MAPK) and Phosphoinositide 3 Kinase (PI3K)-Akt pathways, thus initiating the immune and inflammatory reactions, resulting in a cytokine storm [9, 10]. Mavrilimumab, a potential antagonist of
Load more

Recommended publications
  • Evaluation of Antibody Properties and Clinically Relevant Immunogenicity
    Drug Safety https://doi.org/10.1007/s40264-018-00788-w ORIGINAL RESEARCH ARTICLE Evaluation of Antibody Properties and Clinically Relevant Immunogenicity, Anaphylaxis, and Hypersensitivity Reactions in Two Phase III Trials of Tralokinumab in Severe, Uncontrolled Asthma Mats Carlsson1 · Martin Braddock2 · Yuling Li3 · Jihong Wang3 · Weichen Xu3 · Nicholas White4 · Ayman Megally5 · Gillian Hunter6 · Gene Colice5 © The Author(s) 2019 Abstract Introduction Tralokinumab is a monoclonal antibody (mAb) that neutralizes interleukin (IL)-13, a cytokine involved in the pathogenesis of asthma. Objective The objectives of this study were to characterize the potential immunogenic properties of tralokinumab and report data for anti-drug antibodies (ADAs) and hypersensitivity reactions from two phase III clinical trials. Methods The oligosaccharide structure of tralokinumab, Fab-arm exchange, and ADAs were characterized by standard techniques. Hypersensitivity adverse events (AEs) were evaluated in two pivotal clinical trials of tralokinumab in severe, uncontrolled asthma: STRATOS 1 and 2 (NCT02161757 and NCT02194699). Results No galactose-α-1,3-galactose (α-Gal) epitopes were found in the Fab region of tralokinumab and only 4.5% of glycoforms contained α-Gal in the Fc region. Under non-reducing conditions, Fab-arm exchange did not take place with another immunoglobulin (Ig) G­ 4 mAb (mavrilimumab). However, following glutathione reduction, a hybrid antibody with monovalent bioactivity was detected. ADA incidences (titers) were as follows: STRATOS 1—every 2 weeks (Q2 W) 0.8% (26.0), every 4 weeks (Q4 W) 0.5% (26.0), placebo 0.8% (52.0); STRATOS 2—Q2 W 1.2% (39.0), placebo 0.8% (13.0). Participant-reported hypersensitivity AE rates were as follows: STRATOS 1—Q2 W 25.9%, Q4 W 25.0%, placebo 25.5%; STRATOS 2—Q2 W 13.2%, placebo 9.0%.
    [Show full text]
  • Collaborations on Imaging – the Medimmune’S Innovative Way
    Collaborations on Imaging – The Medimmune’s Innovative Way Jerry Wu, PhD, Medimmune Developments in Healthcare Imaging – Connecting with Industry 18th October 2017 Contents 1 A brief overview of Medimmune 2 Scientific collaborations 3 Scientific Interest Group for Imaging 2 A brief overview of Medimmune Global Biologics Research and Development Arm of ~2,200 Employees in the US and UK Robust pipeline of 120+ Biologics in Research & Development with 40+ projects in Clinical Stage Development California Gaithersburg Cambridge 3 Medimmune – Biologics arm of AstraZeneca Late-stage Discovery and Early Development Development Innovative Medicines and Early Development Unit (Small Molecules) Global Internal and Collaboration and Medicines external combinations Development Market opportunities MedImmune (Biologics) 4 Current therapeutic areas Respiratory, Inflammation and Cardiovascular and Infectious Disease Oncology Autoimmunity Metabolic Disease Neuroscience Main Therapeutic Areas Opportunity-driven Protein Biologics Small Molecules Immuno-therapies Devices Engineering 5 RESPIRATORY, INFLAMMATION AND AUTOIMMUNITY ONCOLOGY (RIA) Medimmune R&D pipeline INFECTIOUS DISEASE (ID), NEUROSIENCE AND CARDIOVASCULAR AND METABOLIC DISEASE (CVMD) GASTROINTESINAL DISEASE PHASE 1 PHASE 2 PHASE 2 PIVOTAL/PHASE 3 Durvalumab + MEDI-573 Durvalumab MEDI-565 MEDI0562 MEDI4276 Durvalumab MEDI0680 Metastatic ≥2nd Line Advanced Solid Tumors Solid Tumors Solid Tumors Stage III NSCLC Solid Tumors Breast Cancer Bladder Cancer Durvalumab/AZD5069/ Durvalmab + MEDI0680
    [Show full text]
  • Study Protocol
    2016N278580_02 CONFIDENTIAL GlaxoSmithKline group of companies 201789 TITLE PAGE Division: Worldwide Development Information Type: Protocol Amendment Title: A Phase 1/2, Double-Blind, Placebo-Controlled Study of the Pharmacokinetics, Safety and Tolerability of GSK3196165 in Combination with Methotrexate Therapy, in Japanese Subjects with Active Moderate-Severe Rheumatoid Arthritis Despite Treatment with Methotrexate. Compound Number: GSK3196165 Development Phase I/II Effective Date: 19- MAY-2017 Protocol Amendment Number: 02 Author(s): PPD Revision Chronology: GlaxoSmithKline Date Version Document Number 2016N278580_00 17-AUG-2016 Original 2016N278580_01 26-SEP-2016 Amendment Number 01 Revision contents: This amendment addresses PMDA modifications requested during the clinical trial notification process. It includes an additional Inclusion Criterion for FVC in Section 5.1; additional Exclusion Criterion and Stopping Criterion for HBV-DNA for subjects with positive anti-HBs antibody in Section 5.2 and Section 5.4; addition of a preventive dose of co-trimoxazole in Section 4.6.1 and Section 6.10.2.2; addition of HBV-DNA test at Screening and addition of footnote for clarification in Section 7.1; addition of “past week’s pain” in Section 12.6.2.1; correction of analysis populations in Section 9.3.1; and deletion of unapproved contraception methods in Japan in Section 12.2. 2016N278580_02 19-MAY-2017 Amendment Number 02 Revision contents: Change of Inclusion Criterion for CRP in Section 5.1. Copyright 2017 the GlaxoSmithKline group of companies. All rights reserved. Unauthorised copying or use of this information is prohibited. 1 2016N278580_02 CONFIDENTIAL 201789 SPONSOR SIGNATORY: Kihito Takahashi Date Vice President, Head of Development and Medical Affairs Division, GlaxoSmithKline K.K.
    [Show full text]
  • Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis
    REVIEW published: 09 July 2021 doi: 10.3389/fimmu.2021.686155 Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis † † Jie Huang 1 , Xuekun Fu 1 , Xinxin Chen 1, Zheng Li 1, Yuhong Huang 1 and Chao Liang 1,2* 1 Department of Biology, Southern University of Science and Technology, Shenzhen, China, 2 Institute of Integrated Bioinfomedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of the population worldwide. With the sustained development of disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing and relieving disease activity in RA patients. Unfortunately, some patients still show limited response to DMARDs, which puts forward new requirements for special targets and novel therapies. Understanding the pathogenetic roles of the various molecules in RA could facilitate discovery of potential therapeutic targets and approaches. In this review, both Edited by: existing and emerging targets, including the proteins, small molecular metabolites, and Trine N. Jorgensen, epigenetic regulators related to RA, are discussed, with a focus on the mechanisms that Case Western Reserve University, result in inflammation and the development of new drugs for blocking the various United States modulators in RA. Reviewed by: Åsa Andersson, Keywords: rheumatoid arthritis, targets, proteins, small molecular metabolites, epigenetic regulators Halmstad University, Sweden Abdurrahman Tufan, Gazi University, Turkey *Correspondence: INTRODUCTION Chao Liang [email protected] Rheumatoid arthritis (RA) is classified as a systemic poly-articular chronic autoimmune joint † disease that primarily affects hands and feet.
    [Show full text]
  • Rheumatoid Arthritis) – Forecast and Market Analysis to 2023
    REFERENCE CODE GDHC509DFR | PUBLICAT ION DATE DECEMBER 2014 MAVRILIMUMAB (RHEUMATOID ARTHRITIS) – FORECAST AND MARKET ANALYSIS TO 2023 MAVRILIMUMAB (RHEUMATOID ARTHRITIS) – FORECAST AND MARKET ANALYSIS TO 2023 Executive Summary The table below presents the key metrics for The major driver for the growth of Mavrilimumab in Mavrilimumab in the 10MM Rheumatoid Arthritis the RA market over the forecast period is: (RA) pharmaceutical markets (US, France, Potential to be a first-in-class therapy. Germany, Italy, Spain, UK, Japan, Australia, China, India) in 2023. Major barrier to the growth of Mavrilimumab in the RA market over the forecast period is: Mavrilimumab: Key Metrics in the 10 Major Pharmaceutical Markets Crowded market, with multiple new entrants Level of Key Events (2013–2023) targeting the same patient population of TNF- Impact Launch of AstraZeneca’s mavrilimumab in inadequate responders. ↑↑ 2020 across the 6MM 2023 Market Sales The figure below illustrates the global US $306.0m Mavrilimumab sales by region during the forecast 5EU $60.4m period. Japan N/A Australia N/A Sales for Mavrilimumab by Region, 2023 China N/A 2023 India N/A Total: $366.3m Total $366.3m 16% Source: GlobalData 10MM = US, France, Germany, Italy, Spain, UK, Japan, Australia, China, and India 6MM = US, France, Germany, Italy, Spain, and UK US 5EU = France, Germany, Italy, Spain, and UK N/A = Not Available 5EU Sales for Mavrilimumab in the Rheumatoid Arthritis Market 84% GlobalData estimates sales of Mavrillimumab at Source: GlobalData the end of the forecast period in 2023, in the US & 5EU at $366.3 million increasing from $145.3 million in 2020.
    [Show full text]
  • Targeting GM-CSF in Rheumatoid Arthritis A.B
    Targeting GM-CSF in rheumatoid arthritis A.B. Avci1, E. Feist2, G.R. Burmester2 1Department of Internal Medicine, ABSTRACT well-known as a haemopoietic growth Rheumatology, Akdeniz University, Granulocyte-macrophage colony-stim- factor used to treat neutropenia follow- Faculty of Medicine, Antalya, Turkey; ulating factor (GM-CSF) is well-known ing chemotherapy. It was a long-time 2Department of Rheumatology and as a haemopoietic growth factor. How- concern that targeted therapies against Clinical Immunology, Charite-University Medicine Berlin, Berlin, Germany. ever, it is also essential in regulating this cytokine could cause severe side functions of mature myeloid cells such effects such as neutropenia or pulmo- Ali Berkant Avci, MD, Assoc. Prof. Eugen Feist, PD Dr as macrophages. Preclinical studies nary alveolar proteinosis. Therefore, Gerd-Rüdiger Burmester, Prof. Dr. and observations of flares of arthritis in during the early development phase Please address correspondence to: patients following GM-CSF treatment of compounds targeting GM-CSF or Ali Berkant Avci, MD, supported its important contribution to its receptor special attention was paid Akdeniz Üniversitesi Hastanesi, the pathogenesis of rheumatoid arthritis to this potential adverse event reveal- İç Hastalıkları AD Romatoloji BD, (RA). As the most advanced compound, ing no evidence for such an associated Kampüs 07059 Konyaaltı/Antalya, mavrilimumab, a monoclonal antibody risk profile. On the other hand the so Turkey. against GM-CSF receptor, has already far available results clearly showed E-mail:[email protected] completed phase II trials with a long rapid and sustained effects on disease Received and accepted on June 29, 2016. term of follow-up period of 74 weeks.
    [Show full text]
  • Immunfarmakológia Immunfarmakológia
    Gergely: Immunfarmakológia Immunfarmakológia Prof Gergely Péter Az immunpatológiai betegségek döntő többsége gyulladásos, és ennek következtében általában szövetpusztulással járó betegség, melyben – jelenleg – a terápia alapvetően a gyulladás csökkentésére és/vagy megszűntetésére irányul. Vannak kizárólag gyulladásgátló gyógyszereink és vannak olyanok, amelyek az immunreakció(k) bénításával (=immunszuppresszió révén) vagy emellett vezetnek a gyulladás mérsékléséhez. Mind szerkezetileg, mind hatástanilag igen sokféle csoportba oszthatók, az alábbi felosztás elsősorban didaktikus célokat szolgál. 1. Nem-szteroid gyulladásgátlók (‘nonsteroidal antiinflammatory drugs’ NSAID) 2. Kortikoszteroidok 3. Allergia-elleni szerek (antiallergikumok) 4. Sejtoszlás-gátlók (citosztatikumok) 5. Nem citosztatikus hatású immunszuppresszív szerek 6. Egyéb gyulladásgátlók és immunmoduláns szerek 7. Biológiai terápia 1. Nem-szteroid gyulladásgátlók (NSAID) Ezeket a vegyületeket, melyek őse a szalicilsav (jelenleg, mint acetilszalicilsav ‘aszpirin’ használatos), igen kiterjedten alkalmazzák a reumatológiában, az onkológiában és az orvostudomány szinte minden ágában, ahol fájdalom- és lázcsillapításra van szükség. Egyes felmérések szerint a betegek egy ötöde szed valamilyen NSAID készítményt. Szerkezetük alapján a készítményeket több csoportba sorolhatjuk: szalicilátok (pl. acetilszalicilsav) pyrazolidinek (pl. fenilbutazon) ecetsav származékok (pl. indometacin) fenoxiecetsav származékok (pl. diclofenac, aceclofenac)) oxicamok (pl. piroxicam, meloxicam) propionsav
    [Show full text]
  • The Two Tontti Tudiul Lui Hi Ha Unit
    THETWO TONTTI USTUDIUL 20170267753A1 LUI HI HA UNIT ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2017 /0267753 A1 Ehrenpreis (43 ) Pub . Date : Sep . 21 , 2017 ( 54 ) COMBINATION THERAPY FOR (52 ) U .S . CI. CO - ADMINISTRATION OF MONOCLONAL CPC .. .. CO7K 16 / 241 ( 2013 .01 ) ; A61K 39 / 3955 ANTIBODIES ( 2013 .01 ) ; A61K 31 /4706 ( 2013 .01 ) ; A61K 31 / 165 ( 2013 .01 ) ; CO7K 2317 /21 (2013 . 01 ) ; (71 ) Applicant: Eli D Ehrenpreis , Skokie , IL (US ) CO7K 2317/ 24 ( 2013. 01 ) ; A61K 2039/ 505 ( 2013 .01 ) (72 ) Inventor : Eli D Ehrenpreis, Skokie , IL (US ) (57 ) ABSTRACT Disclosed are methods for enhancing the efficacy of mono (21 ) Appl. No. : 15 /605 ,212 clonal antibody therapy , which entails co - administering a therapeutic monoclonal antibody , or a functional fragment (22 ) Filed : May 25 , 2017 thereof, and an effective amount of colchicine or hydroxy chloroquine , or a combination thereof, to a patient in need Related U . S . Application Data thereof . Also disclosed are methods of prolonging or increasing the time a monoclonal antibody remains in the (63 ) Continuation - in - part of application No . 14 / 947 , 193 , circulation of a patient, which entails co - administering a filed on Nov. 20 , 2015 . therapeutic monoclonal antibody , or a functional fragment ( 60 ) Provisional application No . 62/ 082, 682 , filed on Nov . of the monoclonal antibody , and an effective amount of 21 , 2014 . colchicine or hydroxychloroquine , or a combination thereof, to a patient in need thereof, wherein the time themonoclonal antibody remains in the circulation ( e . g . , blood serum ) of the Publication Classification patient is increased relative to the same regimen of admin (51 ) Int .
    [Show full text]
  • Antibodies to Watch in 2021 Hélène Kaplona and Janice M
    MABS 2021, VOL. 13, NO. 1, e1860476 (34 pages) https://doi.org/10.1080/19420862.2020.1860476 PERSPECTIVE Antibodies to watch in 2021 Hélène Kaplona and Janice M. Reichert b aInstitut De Recherches Internationales Servier, Translational Medicine Department, Suresnes, France; bThe Antibody Society, Inc., Framingham, MA, USA ABSTRACT ARTICLE HISTORY In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody Received 1 December 2020 therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The Accepted 1 December 2020 coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the KEYWORDS healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two Antibody therapeutics; anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were cancer; COVID-19; Food and authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed Drug Administration; antibodies levilimab and itolizumab had been registered for emergency use as treatments for COVID-19 European Medicines Agency; in Russia and India, respectively. Despite the pandemic, 10 antibody therapeutics had been granted the immune-mediated disorders; first approval in the US or EU in 2020, as of November, and 2 more (tanezumab and margetuximab) may Sars-CoV-2 be granted approvals in December 2020.* In addition, prolgolimab and olokizumab had been granted first approvals in Russia and cetuximab saratolacan sodium was first approved in Japan. The number of approvals in 2021 may set a record, as marketing applications for 16 investigational antibody therapeutics are already undergoing regulatory review by either the FDA or the European Medicines Agency.
    [Show full text]
  • WO 2016/176089 Al 3 November 2016 (03.11.2016) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/176089 Al 3 November 2016 (03.11.2016) P O P C T (51) International Patent Classification: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A01N 43/00 (2006.01) A61K 31/33 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, PCT/US2016/028383 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 20 April 2016 (20.04.2016) SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/154,426 29 April 2015 (29.04.2015) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: KARDIATONOS, INC. [US/US]; 4909 DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, Lapeer Road, Metamora, Michigan 48455 (US).
    [Show full text]
  • Meta-Analysis of Safety of Granulocyte-Macrophage Colony- Stimulating Factor in the Treatment of Rheumatoid Arthritis Rami Diab MD, Mohinder Vindhyal MD
    Meta-analysis of Safety of Granulocyte-Macrophage Colony- Stimulating Factor in the Treatment of Rheumatoid Arthritis Rami Diab MD, Mohinder Vindhyal MD Introduction and Background Results (continued) • Rheumatoid arthritis (RA) is characterized by chronic joint and systemic GM-CSF Placebo inflammation with potential for irreversible joint damage. AAE Total AAE Total • Not uncommonly, resistance to treatment and treatment failures limit adequate disease control. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoeitic growth factor and pro-inflammatory cytokine stimulating proliferation of mature myeloid cells secondarily endorsing inflammatory mediators with the potential to exacerbate RA. • GM-CSF monoclonal antibodies therefore represent an innovative treatment option in refractory RA. The purpose of this meta-analysis was to evaluate the Favors GM-CSF Favors Placebo safety profile of mavrilimumab (Mv) and namilumab (Nm), two novel GM-CSF Fig 1: Forest plot demonstrating statistically significant overall greater likelihood of Any Adverse Event (AAE) in monoclonal antibodies. Mavrilimumab (Mv) and Namilumab (Nm) treated patients combined vs. placebo Methods • PubMed through Oct 2019: Various iterations of keyword and MeSH term searches including GM-CSF Placebo “GM-CSF”, “monoclonal antibodies”, and “rheumatoid arthritis” were performed. AAE Total AAE Total • Selected studies investigated specific GM-CSF monoclonal antibodies in RA patients receiving at least two doses of the study drug and reported on any adverse events (AAEs) in at least one patient over at least six weeks as a primary endpoint. • Secondary endpoints included individual adverse events (IAEs) for each agent. Results Favors GM-CSF Favors Placebo • Eight randomized clinical trials evaluating Mv and Nm GM-CSF monoclonal Fig 2: Forest plot demonstrating statistically significant overall greater likelihood of Any Adverse Event (AAE) in antibodies in 908 subjects were included.
    [Show full text]
  • Efficacy and Safety of Namilumab, a Human Monoclonal Antibody Against Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
    Taylor et al. Arthritis Research & Therapy (2019) 21:101 https://doi.org/10.1186/s13075-019-1879-x RESEARCH ARTICLE Open Access Efficacy and safety of namilumab, a human monoclonal antibody against granulocyte- macrophage colony-stimulating factor (GM-CSF) ligand in patients with rheumatoid arthritis (RA) with either an inadequate response to background methotrexate therapy or an inadequate response or intolerance to an anti-TNF (tumour necrosis factor) biologic therapy: a randomized, controlled trial Peter C. Taylor1* , Didier Saurigny2,9, Jiri Vencovsky3, Tsutomu Takeuchi4, Tadashi Nakamura5, Galina Matsievskaia6, Barbara Hunt7, Thomas Wagner8,11, Bernard Souberbielle2,10 and for the NEXUS Study Group Abstract Background: Namilumab (AMG203), an immunoglobulin G1 monoclonal antibody that binds with high affinity to granulocyte-macrophage colony-stimulating factor (GM-CSF), was evaluated in a phase II randomized, double-blind, placebo-controlled study to investigate the efficacy and safety in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX-IR) or anti-tumour necrosis factor therapy (TNF-IR). Methods: Subcutaneous namilumab (20, 80, or 150 mg) or placebo was administered at baseline and weeks 2, 6, and 10 in patients on stable background methotrexate therapy who were with MTX-IR or TNF-IR. Primary endpoint was mean change from baseline in the 28-joint Disease Activity Score, C-reactive protein version (DAS28-CRP) at week 12 comparing each of the three doses of namilumab to placebo. Safety and tolerability were assessed by adverse events (AEs) and pulmonary parameters. Results were analysed using the per-protocol population. (Continued on next page) * Correspondence: [email protected] 1Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Oxford OX3 7LD, UK Full list of author information is available at the end of the article © The Author(s).
    [Show full text]