Safety and Efficacy of Meplazumab in Patients With Coronary Artery Disease: a Single-center, Triple-blinded, Placebo-controlled, Exploratory, Phase 2, Pilot Trial

The development of coronary atherosclerosis is closely related to inflammation, and CD147 may play an important role in its process. The present study was designed to evaluate the effects of long-term administration of mepolizumab (humanized anti-CD147 antibody) on lipid deposition and inflammation in coronary atherosclerotic plaques in patients with high-risk coronary artery disease, and to preliminarily explore the efficacy, safety, and dosage of long-term administration of mepolizumab in this population.

Start Date16 Oct 2024

Sponsor / Collaborator

Xijing Hospital

NCT06501807 / Not yet recruitingNot ApplicableIIT

Real Life Assessment of Biologics Efficacy in Severe Chronic Rhinosinusitis With Nasal Polyps

With a prevalence of 2-4% in western countries, Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is of major concern regarding its substantial impact on the social and physical quality of life. So far, endoscopic sinus surgery remains the treatment of choice when the first line of medical treatment with corticosteroid has failed.
During the last 15 years, several studies have shown that CRSwNP is associated with a T helper 2 (T2) immune response leading to B cell release of IgE, mucosal recruitment of eosinophils from bone marrow via Interleukin (IL)-5, IL-4 and IL-13 mediated chemoattractant production.
New biologic agents capable of blocking T2 cytokines have been developed in the field of eosinophil-associated diseases, shifting the paradigm of treatment for patients with CRSwNP. In the near future, endotype profiling with accurate biomarkers will be mandatory to tailor the treatment of nasal polyposis with specific biologic therapies.
Herein the investigators propose a prospective study monitoring medical records of CRSwNP patients who undergo biologic treatments. The objectives are to assess treatment efficacy on quality of life, to report clinical and biological criteria for prescription and to measure tolerance and compliance.Patient-reported outcomes will be addressed according to their initial clinical profile (allergy, asthma, NSAID, gastroesophageal reflux disease, obstructive apnea, otologic disorder, smoke habit).

Start Date02 Sep 2024

Sponsor / Collaborator-

CTIS2023-508069-34-01 / RecruitingIIT

Biomarkers for the prediction of individual CRSwNP patients' responses to mepolizumab

Start Date12 Aug 2024

Sponsor / Collaborator-

100 Clinical Results associated with Mepolizumab

100 Translational Medicine associated with Mepolizumab

100 Patents (Medical) associated with Mepolizumab

1,360

Literatures (Medical) associated with Mepolizumab

01 Jan 2025·Joint Bone Spine

Update on targeted treatments for ANCA-associated vasculitis

Article

Author: Puéchal, Xavier

Targeted therapy has revolutionized the management of ANCA-associated vasculitis (AAV) over the last fifteen years. Rituximab, an approved induction and maintenance agent for severe AAV, is no less effective than cyclophosphamide as induction therapy and particularly useful in relapsing or refractory disease, or in women. In patients with relapsing AAV, granulomatosis with polyangiitis or PR3-ANCA, it is more effective than cyclophosphamide. Rituximab maintenance is superior to the conventional immunosuppressive drugs that it replaces. Low-dose preemptive rituximab infusions are recommended every 6months for 18months, followed by re-evaluation to decide whether 4 additional biannual infusions should be administered, balancing the probability of relapse and the risk of serious infections on rituximab. A growing body of experimental and clinical data shows that C5a pathway inhibition is a promising therapeutic option for AAV, which could reduce glucocorticoids needs. Avacopan is a first approved oral C5A receptor antagonist, used when there is a high risk that glucocorticoids will cause serious adverse events. In eosinophilic granulomatosis with polyangiitis, the importance of IL-5 for eosinophil activation and survival led to evaluation and approval of mepolizumab, a humanized monoclonal antibody directed against IL-5. Mepolizumab showed a steroid-sparing effect. Its effectiveness in active vasculitis remains uncertain and is currently being evaluated. Benralizumab targeting the IL-5 receptor was recently shown to be noninferior to mepolizumab. Rituximab has had disappointing results in non-severe active vasculitis and is being evaluated as maintenance therapy. Plasma exchange is not indicated as first-line treatment but remains recommended when creatinine levels exceed 300μmol/L.

31 Dec 2024·Annals of Medicine

Clinical characteristics of complete responders versus non-complete responders to omalizumab, benralizumab and mepolizumab in patients with severe asthma: a long-term retrospective analysis

Article

Author: Martínez-Colls, Mimar ; Cardona Peitx, Gloria ; Pardo, Laura ; Basagaña, Maria ; Abad, Jorge ; Carabias, Lídia ; Padró, Clara ; Cruz, Paula ; Garcia-Olivé, Ignasi ; Navarro, Juan ; Roger, Albert ; Rosell, Antoni ; Martínez-Rivera, Carlos

BACKGROUNDSome patients with severe asthma may benefit from treatment with biologics, but evidence has been mostly collected from randomized controlled trials (RCTs), in which patients' characteristics are different from those encountered in asthma patients in the real-world setting. The aim of this study was to describe the clinical features of complete responders versus non-complete responders to long-term treatment with biologics in patients with severe asthma attended in routine daily practice.METHODSData of a cohort of 90 patients with severe asthma who were treated with biologics (omalizumab, benralizumab, and mepolizumab) for at least 12 months and were followed up to March 2022. Data recorded included clinical characteristics and effectiveness of treatment (exacerbation, Asthma Control Test [ACT] score, lung function, use of maintenance oral corticosteroids [mOCS]), FeNO, and blood eosinophils at baseline, at 12 months, and at the end of follow-up. Complete response is considered if, in addition to not presenting exacerbations or the use of mOCS, the ACT score was >20 and, the FEV₁ >80% predicted.RESULTSAn improvement in all asthma control parameters was observed after 12 months of treatment and a mean follow-up of 55 months. After 12 months of treatment 27.2% of patients met the criteria of complete response and this percentage even increased to 35.3% at the end of follow-up. Long-term complete response was associated to better lung function with mepolizumab and omalizumab treatment and to less previous exacerbations in the benralizumab group. The main cause of not achieving a complete response was the persistence of an airflow obstructive pattern.CONCLUSIONSThis study shows that omalizumab, benralizumab, and mepolizumab improved the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs in the long term follow-up. Airflow obstruction, however, was a predictor of a non-complete response to biologics.

31 Dec 2024·Annals of Medicine

Improvement in health-related quality of life questionnaires with biologic treatment in severe asthma and comorbid chronic rhinosinusitis with or without nasal polyposis: a real-life experience

Article

Author: Santus, Pierachille ; Lorusso, Rosaria ; Busatto, Paolo ; Milani, Lisa ; Casartelli, Anna ; Saad, Marina ; Radovanovic, Dejan ; Danzo, Fiammetta

BACKGROUNDPatients with severe asthma frequently have comorbid chronic rhinosinusitis (CRS) with or without nasal polyps, that can increase the symptom burden and complicate treatment. Real-life clinical data on the impact of biologic treatments on CRS-specific quality-of-life questionnaires are still lacking.MATERIALS AND METHODSIn this retrospective real-life study, we collected data from patients with severe asthma with comorbid CRS with/without nasal polyposis at baseline, and after 3, 6 and 12 months of treatment with omalizumab, mepolizumab, benralizumab or dupilumab. In particular, we evaluated improvements in HRQoL as measured by SinoNasal Outcome Test-22 (SNOT-22, 0 - 110), Visual Analog Scale symptom scores (VAS, 0-10), and Asthma Control Test (ACT, 5-25) and the proportion of patients meeting the minimal clinically important difference (MCID).RESULTSDisease-specific HRQoL, as measured by SNOT 22 and VAS score improved in all patients at 3, 6, and 12 months of treatment compared with baseline (SNOT-22: 14, IQR: 0-52 vs 10, IQR:0-30 vs 0, IQR:0-15 vs 0, IQR:0-12, p < 0.001, VAS score: 1, IQR: 0-5 vs 0, IQR:0-3 vs 0, IQR:0-2 vs 0, IQR 0-1, p < 0.001). After 3 months of treatment >80% of patients reached the MCID for ACT, while only patients on dupilumab showed to reach a MCID in 100% of cases. The effect size depended upon the symptom burden at baseline.CONCLUSIONSThe study confirms the efficacy of omalizumab, mepolizumab, benralizumab, and dupilumab in a real-life setting, with a rapid improvement in CRS-specific HRQoL and general health status. These data highlight the importance of targeting type 2 inflammation in asthmatic patients with co-existing upper and lower airways disease.The Authors disclose that preliminary data and analysis of the present study have been presented in abstract form during the "X International Workshop on Lung Health - Respiratory Disease and Immune Response", held in Nice on 19-21 January 2023.

News (Medical) associated with Mepolizumab

12 Nov 2024

·www.prnewswire.com

Sanofi/Regeneron Pharmaceuticals' DUPIXENT Approval Marks a Significant Shift in Chronic Obstructive Pulmonary Disease Treatment Landscape | DelveInsight

After over a decade without notable progress in treating chronic obstructive pulmonary disease, patients with this ongoing condition now have two new treatment options, with more expected in the future. Regeneron and Sanofi recently revealed that the FDA has expanded the approved uses of their widely successful drug DUPIXENT to include COPD treatment. This marks the drug's sixth approved indication in the US, following its first approval seven years ago for atopic dermatitis. LAS VEGAS, Nov. 12, 2024 /PRNewswire/ -- Chronic obstructive pulmonary disease (COPD) is a progressive lung condition characterized by obstructed airflow, making breathing difficult. It primarily encompasses two main conditions: chronic bronchitis and emphysema, often coexisting. COPD typically develops due to long-term exposure to irritants such as cigarette smoke, air pollution, or occupational dust. As per DelveInsight analysis, the diagnosed prevalent population of COPD in the 7MM was around 44 million in 2023. These cases of COPD in the 7MM are expected to increase at a significant CAGR of 1.4% throughout the study period (2020–2034). As per the estimates, the majority of cases of COPD are in females as compared to males, in the US. But in EU4 and the UK, and Japan the diagnosed cases of males represent the majority of the cases. Overall, in the 7MM, females are predominantly high in number. In 2023, the US had around 3 million, 9 million, 5 million, and 1 million cases of GOLD 1, GOLD 2, GOLD 3, and GOLD 4, respectively based on the severity of airflow limitation. Estimates suggest that airflow limitation was higher in GOLD 2 severity. Various types of medications are used to manage COPD symptoms and complications, including bronchodilators, which help relax the muscles around the airways. This relaxation opens the airways and makes breathing easier. Most bronchodilators are administered via an inhaler. In more severe cases, the inhaler may also contain steroids to reduce inflammation. Some commonly used short-acting and long-acting bronchodilators for COPD management include Albuterol (ProAir HFA, Ventolin HFA, and others), Ipratropium (Atrovent HFA), Levalbuterol (Xopenex), Aclidinium (Tudorza Pressair), Arformoterol (Brovana), and Formoterol (Perforomist). In the LABA category, medications such as Striverdi Respimat, Arcapta/Onbrez, Serevent, and Brovana are included, while the LAMA class features drugs like Spiriva (available as Spiriva HandiHaler and Spiriva Respimat), Tudorza Pressair, Incruse Ellipta, Yupelri, Seebri Neohaler, and Lonhala Magnair. Since the generic version of Brovana was approved in April 2020, its market share has declined. Additionally, Arcapta Neohaler, Seebri Neohaler, and Utibron Neohaler were discontinued in the US in March 2020, which means they no longer contribute to market size. Patients who do not respond to single therapies are often prescribed double or triple therapy. Among the double therapies, the LABA+ICS combination is widely recommended, with drugs such as Symbicort, Breo Ellipta, and Advair. There are also LABA+LAMA combinations, including Anoro Ellipta, Stiolto Respimat, and Bevespi Aerosphere. In July 2020, the US FDA approved AstraZeneca's BREZTRI AEROSPHERE for the maintenance treatment of patients with COPD. Additionally, in October 2020, TRIXEO AEROSPHERE (a combination of formoterol fumarate, glycopyrronium bromide, and budesonide) received marketing authorization in the EU for the maintenance treatment of adult patients with moderate to severe COPD who are not adequately controlled by either a combination of an ICS and LABA or a LABA and LAMA. Currently, two triple combination therapies are available in the US: BREZTRI and TRELEGY ELLIPTA. Learn more about the FDA-approved COPD drugs @ Drugs for COPD Treatment Recently, Sanofi/Regeneron Pharmaceuticals' DUPIXENT added one more jewel to its crown by getting a label expansion nod for COPD from the FDA, EU, and NMPA. DUPIXENT's approval as the first targeted therapy for COPD represents a significant advancement in the treatment landscape for the disease. Unlike conventional treatments, which largely aim to manage symptoms, DUPIXENT specifically targets the IL-4 and IL-13 pathways linked to type 2 inflammation, a key driver in a subset of COPD patients. This precision in targeting allows for a more tailored treatment, especially for patients with elevated eosinophils, who often experience more frequent exacerbations and worse outcomes. The Phase III BOREAS trial demonstrated that patients treated with DUPIXENT experienced a 30% reduction in moderate-to-severe exacerbations over 52 weeks, significant improvements in lung function, and enhanced quality of life. By Week 52, those on DUPIXENT had improved prebronchodilator FEV1 by 160 mL compared to 77 mL in the placebo group. DUPIXENT was also well-tolerated, with a low frequency of adverse events. These results suggest that DUPIXENT could drastically shift COPD management by reducing exacerbations, improving lung function, and offering a safer, targeted therapy for patients with type 2 inflammation. To know more about COPD treatment options, visit @ New Treatment for COPD The chronic obstructive pulmonary disease pipeline possesses potential drugs in mid-stage developments to be launched in the near future. Itepekimab (Sanofi/Regeneron Pharmaceuticals), Benralizumab (AstraZeneca), Tezepelumab (Amgen/AstraZeneca), Mepolizumab (GSK), and others shall further create a positive impact on the market. Discover which therapies are expected to grab major COPD market share @ COPD Market Report Itepekimab is a fully human monoclonal antibody that targets interleukin-33 (IL-33), a protein involved in both type 1 and type 2 inflammation. The drug is administered via subcutaneous injection. Preclinical studies demonstrated that REGN3500 effectively inhibited several markers of both inflammatory types. Regeneron and Sanofi are investigating REGN3500 in diseases related to respiratory and dermatological inflammation. Currently, REGN3500 is in a Phase III clinical trial for COPD and was developed using Regeneron's VelocImmune technology, which produces optimized fully human antibodies. The development is part of a global collaboration between Regeneron and Sanofi. FASENRA (benralizumab) is a humanized recombinant monoclonal antibody of the IgG1k immunoglobulin type that selectively targets the alpha chain of the interleukin 5 receptor (IL-5R) found on eosinophils and basophils. It prevents IL-5 from binding and stops the hetero-oligomerization of the IL-5R's alpha and beta subunits, thereby inhibiting signal transduction. Additionally, it is an afucosylated IgG, which enhances its affinity for the FcγRIIIα receptor on natural killer cells, macrophages, and neutrophils. Approved by the FDA in November 2017 for severe eosinophilic asthma, benralizumab was developed by MedImmune, AstraZeneca's global biologics R&D division. The company is currently conducting Phase III clinical trials for FASENRA as a treatment for COPD. TEZSPIRE (tezepelumab), a pioneering human monoclonal antibody created by Amgen and AstraZeneca, has shown considerable therapeutic potential for various respiratory conditions. Originally intended for treating COPD, TEZSPIRE has yielded encouraging results in decreasing moderate-to-severe exacerbations in patients with high blood eosinophil counts. Recent findings from the Phase IIa COURSE Trial, unveiled at the ATS 2024 conference, underscored TEZSPIRE's effectiveness in minimizing COPD exacerbations among patients with different eosinophil levels. Mepolizumab is currently undergoing Phase III clinical trials for COPD, particularly in patients with frequent exacerbations and elevated eosinophil levels. It is available as an injectable solution and a powder for reconstitution for subcutaneous administration. The IL-5 receptor complex activates several signaling pathways that lead to the release of cytokines, neuromediators, chemokines, and various kinases, which facilitate eosinophil differentiation, proliferation, recruitment, and degranulation. Mepolizumab works by inhibiting the formation of the IL-5 receptor complex, thereby preventing eosinophil activation. This disruption affects normal eosinophil maturation and function, leading to decreased eosinophilic airway inflammation and reduced eosinophil survival. Discover more about drugs for COPD in development @ COPD Clinical Trials The anticipated launch of these emerging therapies for COPD are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the COPD market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for COPD in the 7MM is expected to grow from USD 16 billion in 2023 with a significant CAGR of 5% by 2034. This growth is mainly driven by the rise in the number of prevalent cases of COPD, ongoing clinical research, and better diagnostic tools that might improve the prognosis of the disease. DelveInsight's latest published market report titled as Chronic Obstructive Pulmonary Disease Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the COPD country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The COPD market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent Cases of COPD Subtype-specific Diagnosed Prevalent Cases of COPD Gender-specific Diagnosed Prevalent Cases of COPD Age-specific Diagnosed Prevalent Cases of COPD Diagnosed Prevalent Cases of COPD Based on Severity of Airflow Limitation Diagnosed Prevalent Cases of COPD Based on Symptoms and Exacerbation History The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM COPD market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this COPD market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the COPD market. Also, stay abreast of the mitigating factors to improve your market position in the COPD therapeutic space. Related Reports Chronic Obstructive Pulmonary Disease Pipeline Chronic Obstructive Pulmonary Disease Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key COPD companies, including Sanofi, Chiesi Farmaceutici S.p.A., United Therapeutics Corporation, Verona Pharma plc, Immunotek, Yungjin Pharm. Co., Ltd., Pulmotect, Inc., Tetherex Pharmaceutical, CSL Behring, AstraZeneca, Novartis, Genentech, Vertex Pharmaceuticals, EmeraMed, Afimmune, Mereo BioPharma, Synairgen, Adamis Pharmaceuticals, Quercegen Pharmaceuticals LLC, Regend Therapeutics, Meridigen Biotech Co., Ltd., Pulmatrix, Eisai, GlaxoSmithKline, EpiEndo Pharmaceuticals, 3SBio, OmniSpirant, Foresee Pharmaceuticals, Amgen, Organicell Regenerative Medicine, Arrowhead Pharmaceuticals, ProterixBio, RS BioTherapeutics, MitoRx, C4X Discovery, Respiratorius, ARK biosciences, Incannex, GNI Pharma, Celon pharma, Alveolus Bio, Kinaset therapeutics, Landos Biopharma, Parion Sciences, KeyMed Biosciences, Bioneer corporation, AlgiPharma, Palobiofarma, Dimerix Bioscience, Glenmark Pharmaceuticals, among others. Asthma Market Asthma Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key asthma companies including GlaxoSmithKline, 4D Pharma plc, AstraZeneca, Suzhou Connect Biopharmaceuticals, Avillion, Pearl Therapeutics, ARS Pharmaceuticals, Sinomab, Avalo Therapeutics, Kymab, Sanofi, Cumberland Pharmaceuticals, Genentech, Inc. , among others. Asthma Pipeline Asthma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key asthma companies, including Jiangsu Hengrui Medicine, GlaxoSmithKline, Immunotek SL, AB Science, EMS, Avalo Therapeutics, Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd., ARS Pharmaceuticals, Sanofi, Zura Bio Ltd., AstraZeneca, EURRUS Biotech GmbH, T-Balance Therapeutics GmbH, Gossamer Bio, Aldeyra Therapeutics, Inc., Trio Medicines, Janssen Research & Development, Arrowhead Pharmaceuticals, Hoffman-La-Roche, GlaxoSmithKline, Biohaven Pharmaceutical, TAK-Circulator Co., Shanghai Hengrui Pharmaceutical, among others. Acute Respiratory Distress Syndrome Market Acute Respiratory Distress Syndrome Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key ARDS companies, including MediciNova, Edesa Biotech, Light Chain Biosciences, Boehringer Ingelheim, Genentech, Windtree Therapeutics, Biomarck Pharmaceuticals, Athersys, Healios, Direct Biologics, Biohaven Pharmaceutical, Arch Biopartners, APEPTICO Forschung und Entwicklung GmbH, Staidson (Beijing) Biopharmaceuticals, Veru, Mesoblast Limited, Avalo Therapeutics, Pluristem Therapeutics, ILTOO Pharma, 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] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultDrug ApprovalPhase 3Phase 2

08 Nov 2024

·endpts.com

Amgen and AstraZeneca share positive results in chronic rhinosinusitis

Amgen and AstraZeneca said on Friday that their asthma drug Tezspire reduced nasal congestion and the size of nasal polyps in patients with a different but sometimes related inflammatory condition. Tezspire, also known as tezepelumab, met its co-primary endpoints in a Phase 3 study for patients with chronic rhinosinusitis with nasal polyps, a condition caused by inflammation of the nasal lining that can lead to loss of smell or pressure in the face. The topline results pit the partners against GSK, which reported positive data for its own experimental antibody depemokimab last month. Tezspire would also contend with a handful of biologics already approved for the condition, including Sanofi and Regeneron’s Dupixent, Genentech and Novartis’ Xolair and GSK’s Nucala. Other patients treated with surgery or oral corticosteroids “have a significant side effect profile,” according to Andrew Menzies-Gow, VP of respiratory and immunology on AstraZeneca’s global biopharmaceutical medical team. While Amgen and AstraZeneca have not released any specific data from the Phase 3 trial, the companies said they will present full results to regulators soon, as well as “at an upcoming medical meeting.” Patients in the trial had failed on standard-of-care intranasal corticosteroids. “Tezepelumab has a unique mechanism of action. It targets right at the top of the inflammatory cascade, so it clearly differentiates in its mechanism from the other available drugs,” Menzies-Gow told Endpoints News on Friday. Pablo Panella, AstraZeneca’s global head of respiratory and immunology, added that “we’ll be able to have a more informed discussion” about competition when the companies are able to share the full data. Tezspire was first approved in 2021 as a subcutaneous treatment for severe asthma, followed by another approval in 2023 for a self-administered formulation in a prefilled pen. AstraZeneca and Amgen will seek approval for both formulations in chronic rhinosinusitis with nasal polyps, as “some patients in the US prefer to be administered the drug at the clinic,” Panella said. The drug generated $653 million in combined 2023 sales for Amgen and AstraZeneca.

Clinical ResultPhase 3Drug Approval

08 Nov 2024

·www.businesswire.com

TEZSPIRE met both co-primary endpoints in the Phase III WAYPOINT trial in patients with chronic rhinosinusitis with nasal polyps

WILMINGTON, Del.--( BUSINESS WIRE )--Positive high-level results from the Phase III WAYPOINT trial in patients with chronic rhinosinusitis with nasal polyps (CRSwNP [nasal polyps]) showed that AstraZeneca and Amgen’s TEZSPIRE ® (tezepelumab) demonstrated a statistically significant and clinically meaningful reduction in the size of nasal polyps and reduced nasal congestion compared to placebo. WAYPOINT is a randomized, double-blind trial that evaluated the efficacy and safety of TEZSPIRE administered subcutaneously compared to placebo in adults with severe CRSwNP. Participants in the trial were symptomatic despite treatment with standard of care (intranasal corticosteroids [INCS]). 1 Dr. Joseph Han, Vice Chair of Rhinology & Endoscopic Sinus and Skull Base Surgery, and Allergy, Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, US, and co-primary investigator in the trial, said: “ Chronic rhinosinusitis with nasal polyps negatively impact patients’ daily lives with obstructions leading to disturbances in smell, taste and sleep as well as pain and fatigue. The impressive data from the WAYPOINT trial demonstrate tezepelumab’s potential as a new treatment for patients whose lives are disrupted by this debilitating disease.” Dr. Brian Lipworth, Professor of Allergy and Pulmonology, Scottish Centre for Respiratory Research, and Tayside Rhinology Ear, Nose and Throat Clinic, Ninewells Hospital University of Dundee in Scotland, UK, and co-primary investigator in the trial, said: “ Patients diagnosed with nasal polyps continue to experience significant burden including repeat surgeries and frequent treatment with high doses of oral corticosteroids, which are associated with serious systemic side effects. The tezepelumab data are clinically meaningful and offer patients with nasal polyps hope for a potential new treatment option that may reduce the burden on patients and healthcare systems.” Sharon Barr, Executive Vice President, BioPharmaceuticals R&D said: “ We are excited by the positive results from the Phase III WAYPOINT trial, which show that patients with nasal polyps strongly benefitted from treatment with tezepelumab. These results reinforce that tezepelumab’s first-in-class mode of action, targeting TSLP at the top of the inflammatory cascade, effectively addresses the multiple drivers of epithelial-driven inflammatory diseases.” The safety profile and tolerability of TEZSPIRE in this trial were consistent with the known profile of the medicine. Full results will be shared with regulatory authorities and the scientific community at an upcoming medical meeting. TEZSPIRE is currently approved for the treatment of severe asthma in the US, EU, Japan, and nearly 60 countries across the globe. 2-5 It is approved as a single-use pre-filled syringe and auto-injector for self-administration in the US and EU. 2,3 INDICATIONS AND LIMITATIONS OF USE / ISI TEZSPIRE ® (tezepelumab-ekko) INDICATION TEZSPIRE is indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma. TEZSPIRE is not indicated for the relief of acute bronchospasm or status asthmaticus. CONTRAINDICATIONS Known hypersensitivity to tezepelumab-ekko or excipients. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions were observed in the clinical trials (eg, rash and allergic conjunctivitis) following the administration of TEZSPIRE. Postmarketing cases of anaphylaxis have been reported. These reactions can occur within hours of administration, but in some instances have a delayed onset (ie, days). In the event of a hypersensitivity reaction, consider the benefits and risks for the individual patient to determine whether to continue or discontinue treatment with TEZSPIRE. Acute Asthma Symptoms or Deteriorating Disease TEZSPIRE should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus. Abrupt Reduction of Corticosteroid Dosage Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with TEZSPIRE. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy. Parasitic (Helminth) Infection It is unknown if TEZSPIRE will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with TEZSPIRE. If patients become infected while receiving TEZSPIRE and do not respond to anti-helminth treatment, discontinue TEZSPIRE until infection resolves. Live Attenuated Vaccines The concomitant use of TEZSPIRE and live attenuated vaccines has not been evaluated. The use of live attenuated vaccines should be avoided in patients receiving TEZSPIRE. ADVERSE REACTIONS The most common adverse reactions (incidence ≥3%) are pharyngitis, arthralgia, and back pain. USE IN SPECIFIC POPULATIONS There are no available data on TEZSPIRE use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. Please see full Prescribing Information , including Patient Information and Instructions for Use . You may report side effects related to AstraZeneca products. Notes Chronic Rhinosinusitis with Nasal Polyps (CRSwNP (nasal polyps)) CRSwNP is a complex inflammatory disorder, characterized by persistent inflammation of the nasal mucosa accompanied by benign growths, called nasal polyps. 6,7 Nasal polyps can block nasal passages and lead to breathing problems, difficulty in sense of smell, nasal discharge, facial pain, sleep disturbance and other adverse effects on quality of life. 8-10 Epithelial dysfunction and inflammation are important characteristics of chronic rhinosinusitis and impede the ability of the epithelium to act as a physical and immunological barrier against the external environment. 11 Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that has been implicated in shared pathophysiological processes underlying severe asthma and CRSwNP. 10,12 Current treatments for CRSwNP include intranasal and/or systemic corticosteroids, surgery and biologics. 8,13-16 Phase III WAYPOINT trial WAYPOINT is a double-blind, multi-centre, randomized, placebo-controlled, parallel group trial designed to evaluate the efficacy and safety of tezepelumab in adults with severe CRSwNP. 1 Participants received tezepelumab or placebo, administered via subcutaneous injection. The trial also included a post-treatment follow-up period of 12-24 weeks for participants who completed the 52-week treatment period. 1 The co-primary endpoints of the trial, were change from baseline in total nasal polyp size, measured by the endoscopic total Nasal Polyp Score, and change from baseline in bi-weekly mean nasal congestion, measured by the participant reported Nasal Congestion Score evaluated as part of the daily Nasal Polyposis Symptom Diary. 1 Key secondary endpoints included loss of smell; improvement in disease specific health-related quality of life as measured by SinoNasal Outcome Test (SNOT-22) score; Lund-Mackay score; time to surgery decision and/or systemic corticosteroids for nasal polyposis; time to nasal polyposis surgery decision; time to systemic corticosteroids for nasal polyposis; Nasal Polyposis Symptom Diary total symptom score and, in the population with co-morbid asthma, pre-bronchodilator FEV1 at Week 52. TEZSPIRE TEZSPIRE (tezepelumab) is being developed by AstraZeneca in collaboration with Amgen as a first-in-class human monoclonal antibody that inhibits the action of TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of allergic, eosinophilic and other types of airway inflammation associated with severe asthma, including airway hyperresponsiveness. 17,18 TEZSPIRE is approved in the US, EU, Japan and other countries for the treatment of severe asthma. 19-21 Amgen collaboration In 2020, Amgen and AstraZeneca updated a 2012 collaboration agreement for TEZSPIRE. Both companies will continue to share costs and profits equally after payment by AstraZeneca of a mid single-digit inventor royalty to Amgen. AstraZeneca continues to lead development and Amgen continues to lead manufacturing. All aspects of the collaboration are under the oversight of joint governing bodies. Under the amended agreement, Amgen and AstraZeneca will jointly commercialize TEZSPIRE in North America. Amgen will record product sales in the US, with AZ recording its share of US profits as Collaboration Revenue. Outside of the US, AstraZeneca will record product sales, with Amgen recording profit share as Other/Collaboration revenue. AstraZeneca in Respiratory & Immunology Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals, is a key disease area and growth driver to the Company. AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca . References Clinicaltrials.gov. Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT). Available at: https://clinicaltrials.gov/ct2/show/NCT04851964 . [Last accessed: November 2024]. Tezspire (tezepelumab) US prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761224s003lbl.pdf . [Last accessed: November 2024]. Tezspire (tezepelumab) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/tezspire-epar-product-information_en.pdf . [Last accessed: November 2024]. AstraZeneca plc. Tezspire approved in Japan for the treatment of severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-japan-for-severe-asthma.html [Last accessed: November 2024]. Data on File. AstraZeneca. 2024. REF-251231. Bachert C, et al . Phenotypes and Emerging Endotypes of Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2016; 4 (4): 621-628. Del Toro E, Portela J. Nasal Polyps. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560746/ [Last accessed: November 2024]. Stevens WW, et al . Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract . 2016; 4 (4): 565-572. Abdalla S, et al . Prevalence of sinonasal outcome test (SNOT-22) symptoms in patients undergoing surgery for chronic rhinosinusitis in the England and Wales National prospective audit. Clin Otolaryngol . 2012; 37 (4): 276-282. Laidlaw TM, et al . Chronic Rhinosinusitis with nasal polyps and asthma. J Allergy Clin Immunol Pract 2021;9:1133–1141. Wynne M, et al . Contribution of epithelial cell dysfunction to the pathogenesis of chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy . 2019;33:782–790. Liao B, et al. Interaction of thymic stromal lymphopoietin, IL-33, and their receptors in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps. Allergy . 2015;70:1169–1180. Xolair (omalizumab) Summary of Product Characteristics; Available at: https://www.ema.europa.eu/en/documents/product-information/xolair-epar-product-information_en.pdf [Last accessed November 2024]. Xolair (omalizumab) US prescribing information; Available at: https://www.gene.com/download/pdf/xolair_prescribing.pdf [Last accessed: November 2024]. Nucala (mepolizumab) US prescribing information; Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761122s006,125526s018lbl.pdf . [Last accessed November 2024]. Dupixent (dupilumab) US prescribing information; Available at: https://www.regeneron.com/downloads/dupixent_fpi.pdf . [Last accessed: November 2024]. Corren J , et al . Tezepelumab in adults with uncontrolled asthma . N Engl J Med . 2017;377:936-946. Varricchi G, et al . Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol . 2018;9:1595. AstraZeneca plc. Tezspire (tezepelumab) approved in the US for severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/tezspire-tezepelumab-approved-in-the-us-for-severe-asthma.html . [Last accessed: November 2024]. AstraZeneca plc. Tezspire approved in the EU for the treatment of severe asthma. 2022. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/tezspire-approved-in-the-eu-for-the-treatment-of-severe-asthma.html . [Last accessed: November 2024]. AstraZeneca plc. Tezspire approved in Japan for the treatment of severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-japan-for-severe-asthma.html . [Last accessed: November 2024].

Clinical ResultPhase 3Drug ApprovalLicense out/in

100 Deals associated with Mepolizumab

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KEGG	Wiki	ATC	Drug Bank
D04923	Mepolizumab	R03DX09	DB06612

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Granulomatosis With Polyangiitis	CN	GlaxoSmithKline Trading Services Ltd.	19 Nov 2021
Eosinophilic Granuloma	JP	GlaxoSmithKline KK	25 Mar 2020
Eosinophilic Asthma	KR	GSK Plc	01 Apr 2016
Chronic rhinosinusitis with nasal polyps	NO	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Chronic rhinosinusitis with nasal polyps	EU	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Chronic rhinosinusitis with nasal polyps	LI	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Chronic rhinosinusitis with nasal polyps	IS	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Churg-Strauss Syndrome	EU	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Churg-Strauss Syndrome	NO	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Churg-Strauss Syndrome	IS	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Churg-Strauss Syndrome	LI	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Hypereosinophilic Syndrome	IS	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Hypereosinophilic Syndrome	EU	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Hypereosinophilic Syndrome	NO	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Hypereosinophilic Syndrome	LI	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Pulmonary Eosinophilia	NO	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Pulmonary Eosinophilia	IS	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Pulmonary Eosinophilia	LI	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Pulmonary Eosinophilia	EU	GlaxoSmithKline Trading Services Ltd.	01 Dec 2015
Asthma	US	GlaxoSmithKline LLC	04 Nov 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypereosinophilic Syndrome	Phase 3	US	GSK Plc	23 Mar 2004
Hypereosinophilic Syndrome	Phase 2	CA	GSK Plc	23 Mar 2004
Hypereosinophilic Syndrome	Phase 1	AU	GSK Plc	23 Mar 2004
Hypereosinophilic Syndrome	Phase 1	CA	GSK Plc	23 Mar 2004
Hypereosinophilic Syndrome	Phase 1	CH	GSK Plc	23 Mar 2004
Hypereosinophilic Syndrome	Phase 1	CH	GSK Plc	23 Mar 2004
Hypereosinophilic Syndrome	Discovery	AU	GSK Plc	23 Mar 2004

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00244686 (Pubmed) Manual	Phase 3	Severe asthma	514	Mepolizumab 100 mg SC (Adults/adolescents (≥12 years of age))	(wtpvviuonb) = rttruxpgdz coswqkmfwo (ywbmhfhkdk )	Positive	28 Oct 2024
				Mepolizumab 40 mg or 100 mg SC (bodyweight <40 or ≥40 kg, respectively) (Pediatric patients (6-11 years of age))	-
NCT04133909 (MATINEE, NEWS) Manual	Phase 3	Pulmonary Disease, Chronic Obstructive	-	Nucala	dvntlezpql(cjtqjgwump) = The trial met its primary endpoint. oyclaapwrt (cqageebgik ) Met View more	Positive	06 Sep 2024
				Placebo
EULAR2024 Manual	Not Applicable	Churg-Strauss Syndrome Maintenance \| Induction IL-5	48	Mepolizumab (maintenance phase for relapsing and refractory EGPA)	lngngmdhdm(wzgwpyyoqi) = oglnpfakqk kuuhqdsiqc (lpanmhvtpj ) View more	Positive	05 Jun 2024
				Mepolizumab (in the remission induction phase for severe EGPA)	lngngmdhdm(wzgwpyyoqi) = gxtjxicuwl kuuhqdsiqc (lpanmhvtpj ) View more
EULAR2024 Manual	Not Applicable	Eosinophilic Granuloma interleukin 5 (IL-5) \| IL-5α receptor	67	Mepolizumab 300 mg	(nzpclxnthe) = tsjntqlbjw pheiprrcxt (xgohheiehz ) View more	Positive	05 Jun 2024
				Mepolizumab 100 mg	(nzpclxnthe) = ixaezyaaos pheiprrcxt (xgohheiehz ) View more
EULAR2024	Not Applicable	Churg-Strauss Syndrome	-	Mepolizumab 300mg	tojydowyhm(qmyoiphvme) = A total of 118 patients were enrolled, 91% completed the study and 9% discontinued treatment. Of these, 55% were female, the mean (standard deviation [SD]) age was 62 (13.2) years and the mean (SD) time since diagnosis was 5.6 (4.4) years. Over 99% of patients had comorbidities at baseline (28% osteoporosis; 22% hypertension; 15% hyperlipidemia). Most patients (97%) used 300mg mepolizumab with a mean (SD) duration of 4.2 (0.68) years during the treatment period; 2 patients who continued from the MIRRA trial (NCT04551989) used mepolizumab for ≤7.4 years. AEs were reported in 69 patients (58%) and SAEs were reported in 26 patients (22%) over the observation period, infections were the most commonly reported (AEs: 36 patients [31%]; SAEs: 8 patients [7%]). There were no drug-related AEs. zxfklombnb (yjqceksuaa )	-	05 Jun 2024
EULAR2024	Not Applicable	Churg-Strauss Syndrome Maintenance	5	Rituximab and Mepolizumab combination	bsolailxte(zxacaobtil) = 3/5 patients tyjrynkatl (jycgxklwfi ) View more	Positive	05 Jun 2024
EULAR2024	Not Applicable	Churg-Strauss Syndrome Maintenance MPO-ANCA-associated vasculitis (MPO-AAV)	25	MEPOLIZUMAB (Early administration group)	yszsaqeegt(sjbjzmcskd) = 0 in both groups cdscpbqvzr (jrihzivtnr ) View more	Positive	05 Jun 2024
				MEPOLIZUMAB (During maintenance group)
NCT03298061 (LAP/MEA116841, ATS2024) Manual	Phase 3	Granulomatosis With Polyangiitis	100	Mepolizumab	(kztzwjzhpy) = hthtkcqrex wwnzplthph (qgmpjxnxke )	Positive	19 May 2024
EHA2024	Not Applicable	Hypereosinophilic Syndrome Second line PDGFRΑ-negative	3	Mepolizumab	vkgwuujwxt(dpicrdoyga) = oueaqiwuvt ugbggsbaat (ibflbgsbhw )	Positive	14 May 2024
NCT03298061 (MEA116841 \| LAP/MEA116841, CTgov)	Phase 3	Churg-Strauss Syndrome	100	Mepolizumab	(gkucwjgeix) = auhtqmwzuj bjqrznnyii (uuixefwcdu, xwtlsetimd - utvnofibdn) View more	-	12 Mar 2024

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