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Janice M Reichert
Over 50 investigational monoclonal antibody (mAb) therapeutics are currently undergoing evaluation in late-stage clinical studies, which is expected to drive a trend toward first marketing approvals of at least 6-9 mAbs per year in the near-term. In the United States (US), a total of 6 and 9 mAbs were granted first approvals during 2014 and 2015, respectively; all these products are also approved in the European Union (EU). As of December 1, 2016, 6 mAbs (atezolizumab, olaratumab, reslizumab, ixekizumab, bezlotoxumab, oblitoxaximab) had been granted first approvals during 2016 in either the EU or US...
February 2017: MAbs
B Popovic, J Breed, D G Rees, M J Gardener, L M K Vinall, B Kemp, J Spooner, J Keen, R Minter, F Uddin, G Colice, T Wilkinson, T Vaughan, R D May
Interleukin (IL)-13 is a pleiotropic T helper type 2 cytokine frequently associated with asthma and atopic dermatitis. IL-13-mediated signalling is initiated by binding to IL-13Rα1, which then recruits IL-4Rα to form a heterodimeric receptor complex. IL-13 also binds to IL-13Rα2, considered as either a decoy or a key mediator of fibrosis. IL-13-neutralising antibodies act by preventing IL-13 binding to IL-13Rα1, IL-4Rα and/or IL-13Rα2. Tralokinumab (CAT-354) is an IL-13-neutralising human IgG4 monoclonal antibody that has shown clinical benefit in patients with asthma...
December 9, 2016: Journal of Molecular Biology
T Karelina, V Voronova, O Demin, G Colice, B M Agoram
Emerging T-helper type 2 (Th2 ) cytokine-based asthma therapies, such as tralokinumab, lebrikizumab (anti-interleukin (IL)-13), and mepolizumab (anti-IL-5), have shown differences in their blood eosinophil (EOS) response. To better understand these effects, we developed a mathematical model of EOS dynamics. For the anti-IL-13 therapies, lebrikizumab and tralokinumab, the model predicted an increase of 30% and 10% in total and activated EOS in the blood, respectively, and a decrease in the total and activated EOS in the airways...
November 2016: CPT: Pharmacometrics & Systems Pharmacology
Diego Bagnasco, Matteo Ferrando, Gilda Varricchi, Giovanni Passalacqua, Giorgio Walter Canonica
Asthma is a high-prevalence disease, still accounting for mortality and high direct and indirect costs. It is now recognized that, despite the implementation of guidelines, a large proportion of cases remain not controlled. Certainly, adherence to therapy and the education of patients remain the primary objective, but the increasingly detailed knowledge about the pathogenic mechanisms and new biotechnologies offer the opportunity to better address and treat the disease. Interleukin (IL)-13 and IL-4 appear as the most suitable targets to treat the T helper 2 (TH2)-mediated forms (endotypes) of asthma...
2016: International Archives of Allergy and Immunology
Ibrahim Sulaiman, Jonathan Chee Woei Lim, Hon Liong Soo, Johnson Stanslas
Extensive research into the therapeutics of asthma has yielded numerous effective interventions over the past few decades. However, adverse effects and ineffectiveness of most of these medications especially in the management of steroid resistant severe asthma necessitate the development of better medications. Numerous drug targets with inherent airway smooth muscle tone modulatory role have been identified for asthma therapy. This article reviews the latest understanding of underlying molecular aetiology of asthma towards design and development of better antiasthma drugs...
October 2016: Pulmonary Pharmacology & Therapeutics
Renata Rubinsztajn, Ryszarda Chazan
Asthma is a heterogeneous inflammatory disease. Most patients respond to current standard of care, i.e., bronchodilators, inhaled glucocorticosteroids and other anti-inflammatory drugs, but in some adequate asthma control cannot be achieved with standard treatments. These difficult-to-treat patients would be the target population for new biological therapies. At present, omalizumab is the only biological agent approved for the treatment of early-onset, severe IgE-dependent asthma. It is safe, effective, and well tolerated...
2016: Advances in Experimental Medicine and Biology
Christopher E Brightling, Pascal Chanez, Richard Leigh, Paul M O'Byrne, Stephanie Korn, Dewei She, Richard D May, Katie Streicher, Koustubh Ranade, Edward Piper
BACKGROUND: Interleukin 13 is a central mediator of asthma. Tralokinumab is a human interleukin-13 neutralising monoclonal antibody. We aimed to assess the efficacy and safety of two dosing regimens of tralokinumab in patients with severe uncontrolled asthma. METHODS: We did a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 2b study at 98 sites in North America, South America, Europe, and Asia. Patients aged 18-75 years with severe asthma and two to six exacerbations in the previous year were randomly assigned (1:1), via an interactive voice-response or web-response system, to one of two dosing regimen groups (every 2 weeks, or every 2 weeks for 12 weeks then every 4 weeks) and further randomised (2:1), via computer-generated permuted-block randomisation (block size of six), to receive tralokinumab 300 mg or placebo for 1 year...
September 2015: Lancet Respiratory Medicine
Paul G Baverel, Meena Jain, Iwona Stelmach, Dewei She, Balaji Agoram, Sara Sandbach, Edward Piper, Piotr Kuna
AIMS: Tralokinumab, an investigational human immunoglobulin G4 monoclonal antibody, potently and specifically neutralizes interleukin-13, a central mediator of asthma. Tralokinumab has shown improvements in clinical endpoints in adults with uncontrolled asthma. The present study explored the pharmacokinetics (PK) and safety of a single tralokinumab dose, and utilized a population PK modelling and simulation approach to evaluate the optimal dosing strategy for adolescents. METHODS: Adolescent subjects with asthma, using daily controller medication, received a single subcutaneous dose of tralokinumab 300 mg...
December 2015: British Journal of Clinical Pharmacology
Silvio Danese, Janusz Rudziński, Wolfgang Brandt, Jean-Louis Dupas, Laurent Peyrin-Biroulet, Yoram Bouhnik, Dariusz Kleczkowski, Peter Uebel, Milan Lukas, Mikael Knutsson, Fredrik Erlandsson, Mark Berner Hansen, Satish Keshav
OBJECTIVE: Interleukin-13 (IL-13) has been implicated as a key driver of UC. This trial evaluates the efficacy and safety of tralokinumab, an IL-13-neutralising antibody, as add-on therapy in adults with moderate-to-severe UC despite standard treatments. DESIGN: Non-hospitalised adults with UC (total Mayo score ≥6) were randomised to receive tralokinumab 300 mg or placebo subcutaneously every 2 weeks for 12 weeks. The primary end point was the rate of clinical response at week 8...
February 2015: Gut
Lynne A Murray, Huilan Zhang, Sameer R Oak, Ana Lucia Coelho, Athula Herath, Kevin R Flaherty, Joyce Lee, Matt Bell, Darryl A Knight, Fernando J Martinez, Matthew A Sleeman, Erica L Herzog, Cory M Hogaboam
The aberrant fibrotic and repair responses in the lung are major hallmarks of idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been used in the clinic with limited success, raising the possibility that an effective therapeutic strategy in this disease must inhibit fibrosis and promote appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF, but its disease association and mechanism of action remains unknown. In the present study, an overexpression of IL-13 and IL-13 pathway markers was associated with IPF, particularly a rapidly progressive form of this disease...
May 2014: American Journal of Respiratory Cell and Molecular Biology
Nathan Hambly, Parameswaran Nair
PURPOSE OF REVIEW: A small proportion of patients with asthma have severe disease characterized by persistent airflow obstruction, airway hyperresponsiveness and eosinophilic airway inflammation. This review focuses on the clinical efficacy of inhibiting T helper 2-cytokine-mediated inflammatory responses using monoclonal antibodies directed against immunoglobulin E (IgE), interleukin (IL)-5, and IL-4/IL-13 in patients with severe refractory asthma. RECENT FINDINGS: The heterogeneity of airway inflammation in severe asthma has led to the recognition of multiple pathophysiologically distinct severe asthma endotypes...
January 2014: Current Opinion in Pulmonary Medicine
Ileana Antohe, Rodica Croitoru, Sabina Antoniu
INTRODUCTION: Asthma is a chronic inflammatory disease of the airways mainly related to allergen exposure, in which various cytokine-specific pathways interact among themselves to promote IgE hyperproduction, bronchial hyperresponsiveness, eosinophil local recruitment and airways remodeling. IL-13 is known for its prominent pathogenic role in this disease and therapeutic blocking approaches are underway. AREAS COVERED: Anti-IL-13 antibodies are currently investigated in clinical studies in uncontrolled asthma...
February 2013: Expert Opinion on Biological Therapy
Edward Piper, Christopher Brightling, Robert Niven, Chad Oh, Raffaella Faggioni, Kwai Poon, Dewei She, Chris Kell, Richard D May, Gregory P Geba, Nestor A Molfino
Pre-clinical data demonstrate a pivotal role for interleukin (IL)-13 in the development and maintenance of asthma. This study assessed the effects of tralokinumab, an investigational human IL-13-neutralising immunoglobulin G4 monoclonal antibody, in adults with moderate-to-severe uncontrolled asthma despite controller therapies. 194 subjects were randomised to receive tralokinumab (150, 300 or 600 mg) or placebo subcutaneously every 2 weeks. Primary end-point was change from baseline in mean Asthma Control Questionnaire score (ACQ-6; ACQ mean of six individual item scores) at week 13 comparing placebo and combined tralokinumab dose groups...
February 2013: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Garry M Walsh
Biopharmaceutical approaches have been used to target key elements in the processes controlling airway inflammation in asthma and COPD. There is compelling evidence that IL-13 is a key mediator in the inflammatory processes in the asthmatic lung. Tralokinumab (CAT-354), under development by MedImmune, is an injectable, anti-IL-13 humanized mAb for the potential treatment of asthma and COPD. In a study in mice, tralokinumab prevented the development of the asthmatic phenotype, including eosinophil recruitment and airway hyperresponsiveness...
November 2010: Current Opinion in Investigational Drugs
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