IL-5Rα

FASENRA enabled patients to taper off oral corticosteroids while preventing relapses WILMINGTON, Del.--(BUSINESS WIRE)-- Positive results from the MANDARA Phase III trial for FASENRA® (benralizumab) in patients with EGPA were published in the New England Journal of Medicine today,1 as the first head-to-head trial of biologics in patients with EGPA,2 and the first to demonstrate that more than half of patients achieved remission with eosinophil-targeting biologic therapies.1 These findings were also presented today as a late-breaking poster at the American Academy of Allergy Asthma & Immunology (AAAAI) Annual Meeting in Washington, DC, February 23-26.3 MANDARA compared benralizumab to mepolizumab in patients with EGPA receiving oral corticosteroids (OCS) with or without stable immunosuppressive therapy.2 Patients were randomized to receive either a single 30 mg subcutaneous injection of benralizumab, or three separate 100 mg subcutaneous injections of mepolizumab, once every four weeks.2 Full results showed that benralizumab met the primary endpoint of the trial and demonstrated non-inferior rates of remission compared to mepolizumab.1 The primary endpoint of adjusted rate of remission was 59% for benralizumab-treated patients at weeks 36 and 48, compared with 56% for mepolizumab (difference in rates: 3%; 95% CI:, –13,18).1 Remission in EGPA is defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS dose less than or equal to 4 mg/day.2 A higher proportion of FASENRA-treated patients were able to fully taper off OCS during weeks 48 through 52 (41% in the benralizumab arm vs. 26% in the comparator arm (difference: 16%; 95% CI: 1,31).1 Additionally, 86% of benralizumab patients vs. 74% in the comparator arm (difference: 12%; 95% CI: −1, 25) had at least a 50% reduction in OCS dose during weeks 48 through 52.1 Dr. Michael Wechsler, Professor of Medicine and Director of The Asthma Institute at National Jewish Health, and International Coordinating Investigator of the MANDARA trial said: “Patients with EGPA typically rely on long-term, high-dose OCS, which can cause serious and lasting side effects, and often suffer recurrent relapses when attempting to taper off their treatment. These findings are an exciting step forward as they affirm that eosinophil-targeting biologic treatments helped more patients achieve remission and taper off of steroid therapy.” Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca said, “The results from this trial are an important step forward for the EGPA community, as this is the first trial to demonstrate that remission from EGPA with an eosinophil-targeting biologic is achievable for the majority of patients. This is a significant advancement and shows that benralizumab helped patients achieve remission and reduce chronic OCS usage, in a convenient, single, monthly subcutaneous injection, and could alleviate some of the impact of this debilitating disease.” Elevated levels of eosinophils play a central role in EGPA disease pathophysiology.4 All patients with EGPA have very high levels of eosinophils at some point in their disease, both in peripheral blood and in affected tissues or organs.5,6 Approximately half of patients with EGPA have concomitant, adult-onset severe eosinophilic asthma, and often have sinus and nasal symptoms.5,7 FASENRA has a unique mode of action that leads to near complete depletion of eosinophils.8,9 Treatment with benralizumab was associated with a greater reduction of blood eosinophil counts from week 1 compared to mepolizumab and maintained at all timepoints.1 At week 1 mean blood eosinophil count ratio to baseline was 0.15 vs. 0.39 respectively (adjusted geometric mean ratio: 0.38; 95% CI: 0.29, 0.49) and 0.10 vs. 0.26 at week 52 (adjusted geometric mean ratio: 0.36; 95% CI: 0.27, 0.49).1 Benralizumab was well tolerated with no new safety signals, which is consistent with the known pro the medicine.1 FASENRA is currently approved as an add-on maintenance treatment for SEA in 80 countries including the US, Japan and in the EU, and is approved for self-administration in the US, EU and other countries.10-13 AstraZeneca has been working with regulatory authorities around the world in order to bring benralizumab to EGPA patients as quickly as possible. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Known hypersensitivity to benralizumab or excipients. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. These reactions generally occur within hours of administration, but in some instances have a delayed onset (ie, days). Discontinue in the event of a hypersensitivity reaction. Acute Asthma Symptoms or Deteriorating Disease FASENRA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm. Reduction of Corticosteroid Dosage Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. 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 FASENRA will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to anti-helminth treatment, discontinue FASENRA until infection resolves. ADVERSE REACTIONS The most common adverse reactions (incidence ≥ 5%) include headache and pharyngitis. Injection site reactions (eg, pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo. USE IN SPECIFIC POPULATIONS A pregnancy exposure registry monitors pregnancy outcomes in women exposed to FASENRA during pregnancy. To enroll call 1-877-311-8972 or visit . The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. INDICATION FASENRA is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. FASENRA is not indicated for treatment of other eosinophilic conditions FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus Please read full Prescribing Information, including Patient Information and Instructions for Use. You may report side effects related to AstraZeneca products. Notes Eosinophilic granulomatosis with polyangiitis EGPA, formerly known as Churg-Strauss Syndrome, is a rare, immune-mediated inflammatory disease that is caused by inflammation of small to medium-sized blood vessels.4,5 It is estimated that 118,000 people throughout the world live with EGPA.14 EGPA can result in damage to multiple organs, including lungs, upper airway, skin, heart, gastrointestinal tract and nerves.5 The most common symptoms and signs include extreme fatigue, weight loss, muscle and joint pain, rashes, nerve pain, sinus and nasal symptoms, and shortness of breath.5,6 Without treatment, the disease may be fatal.5,6 Almost half (47%) of patients do not achieve remission with current treatments.15 There are limited treatment options for EGPA. Patients are often treated with chronic high-dose OCS and experience recurrent relapses when attempting to taper off OCS.6,16 Mepolizumab is currently the only approved treatment for EGPA.17 MANDARA MANDARA was a randomized, double blind, double-dummy, active-controlled, parallel group, multicentre 52-week Phase III trial which compared the efficacy and safety of FASENRA to mepolizumab in adult patients with relapsing or refractory EGPA.2 In the blinded trial, 140 patients were randomized 1:1 (70 per treatment group) to receive either a single 30mg subcutaneous injection of FASENRA or three separate 100mg subcutaneous injections of mepolizumab once every four weeks.1 The primary endpoint was the proportion of patients who were in remission at both weeks 36 and 48.2 Remission is defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS dose less than or equal to 4 mg/day.2 FASENRA remission was compared to the historical placebo rate from mepolizumab’s Phase III trial, MIRRA.18 The primary statistical analysis was to demonstrate non-inferiority of FASENRA versus mepolizumab based on the primary endpoint.1 All patients who complete the 52-week double-blind treatment period were eligible to continue into an ongoing open label extension (OLE) period, intended to allow each patient at least one year of treatment with open-label FASENRA.2 Mepolizumab is a humanized IL-5 antagonist monoclonal antibody.3 FASENRA FASENRA is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of blood and tissue eosinophils in most patients via apoptosis (programmed cell death).8,9 FASENRA (benralizumab) is currently approved in more than 80 countries, including the US, EU, Japan, and is approved for self-administration in the US, EU and other countries.10-13 FASENRA has been prescribed to over 120,000 patients globally.19 FASENRA is in development for other diseases including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome.20-22 FASENRA was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan. 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 (LSE/STO/Nasdaq: AZN) 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 operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit and follow the Company on social media @AstraZeneca. References 1. Wechsler ME, et al. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2024. 2. Clinicaltrials.gov. Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab. (MANDARA). Available at: . [Last accessed: January 2024]. 3. Late Breaking Abstracts Presented at Scientific Sessions 2024 AAAAI Annual Meeting February 23-26, 2024. Available at: Advance/journals/ymai/AAAAI_2024_LateBreaking_Abstracts-1707140446317.pdf. [Last accessed: February 2024]. 4. Furuta S, et al. Update on eosinophilic granulomatosis with polyangiitis. Allergol Int. 2019;68:430-436. 5. American Partnership for Eosinophilic Disorders. Eosinophilic Granulomatosis with Polyangiitis (EGPA). Available at: . [Last accessed: January 2024]. 6. Baldini C, et al. Clinical Manifestations and Treatment of Churg-Strauss Syndrome. Rheum Dis Clin N Am. 2010;36:527–543. 7. Cottin V, et al. Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg–Strauss). Eur Respir J. 2016;48:1429-1441. 8. Kolbeck R, et al. MEDI-563, a humanized anti-IL-5 receptor a mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125:1344-1353.e2. 9. Pham TH, et al. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21-29. 10. AstraZeneca news release. Available at: . [Last accessed: January 2024]. 11. AstraZeneca news release. Available at: . [Last accessed: January 2024]. 12. AstraZeneca Annual Report 2023. Available at: . [Last accessed: February 2024]. 13. AstraZeneca news release. Fasenra met the primary endpoint in the MANDARA Phase III trial in eosinophilic granulomatosis with polyangiitis (EGPA). Available at: )%20who%20were%20receiving%20oral. [Last accessed: February 2024]. 14. AstraZeneca Data on file. 2022. REF-167820. 15. Wechsler ME, et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017:376;1921-1932. 16. Bell CF, et al. Burden of illness and costs associated with eosinophilic granulomatosis with polyangiitis: evidence from a managed care database in the United States. J Manag Care Spec Pharm. 2021;27(9):1249-1259. 17. Mepolizumab US prescribing information. Available from: [Last accessed: January 2024]. 18. AstraZeneca Data on file. 2023. REF-196096. 19. AstraZeneca Data on File. 2022. REF-153839 20. Clinicaltrials.gov. Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations (RESOLUTE). Available from: . [Last accessed: September 2023]. 21. Clinicaltrials.gov. Efficacy and Safety Study of Benralizumab in Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID). Available at: . [Last accessed: January 2024]. 22. Clinicaltrials.gov. A Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (NATRON). Available from: . [Last accessed: January 2024]. Veeva ID: Z4-61457 Date of Preparation: Feb 2024

AstraZeneca is touting a trial win for Fasenra in eosinophilic granulomatosis with polyangiitis as it works to add to the drug's label. Competing to treat patients with severe eosinophilic asthma (SEA), AstraZeneca has fared well matching its IL-5 inhibitor Fasenra up against GSK’s Nucala. But AZ has stumbled in its efforts to add indications to Fasenra's label. In 2022, the FDA rejected the medicine to treat rhinosinusitis. Then, later in the year, shaky trial data derailed the company’s bid for an approval in eosinophilic esophagitis (EoE). On Monday, however, the company revealed positive news for Fasenra as it has achieved its primary endpoint in the phase 3 MANDARA trial, demonstrating noninferior rates of remission in a head-to-head battle against Nucala in patients with eosinophilic granulomatosis with polyangiitis (EGPA). AZ did not provide numbers with the trial results. Those will come at a future medical conference, the company said. With a 2017 label expansion, Nucala is the only treatment approved for EGPA. In proving noninferiority to Nucala, AZ's Fasenra did so with a smaller dosing regimen—one 30-mg subcutaneous injection every four weeks versus three 100-mg injections of Nucala over the same period. While the dosing edge is one positive for AZ's drug, remission is the primary focus for the company. “Our goal is to make remission a treatment goal for every patient with severe asthma and with EGPA,” Andrew Menzies-Gow, AZ’s global medical head of respiratory biologics, said in an interview. “We feel that’s a goal that will dramatically shift how patients are treated today.” Asthma patients typically take on additional treatments as the severity of their disease increases, Menzies-Gow said. But with Fasenra’s ability to control disease, patients can be weaned off the added therapies.  This week at the European Respiratory Society (ERS) International Congress in Milan, AZ is presenting evidence from the SHAMAL phase 4 trial showing that Fasenra allows for reduction in background treatment. Of the 168 SEA patients in the trial’s tapering arm, 92% maintained disease control and remained exacerbation-free despite a decrease in inhaled corticosteroid therapy. Also at the ERS meeting, AZ presented data that showed Fasenra’s ability to sustain remission. In the BORA phase 3 extension study, of the nearly 1 in 3 SEA patients who achieved remission through 12 months of treatment, 73% remained so for another 12 months.  “This concept of remission is particularly central across our biologics portfolio, across a number of diseases,” Pablo Panella, AZ’s senior vice president, global respiratory, said in the interview. “We believe that this can have a profound impact in increasing the access to biologics in the class as a whole.” In coming up short in a trial of EoE patients last year, Fasenra cleared the remission bar, topping placebo. But it failed to meet its other objective, which was to relieve swallowing issues (dysphagia) that come with the disorder. As for EGPA, which was formerly known as Churg-Strauss syndrome, the condition is a rare immune-mediated vasculitis that can damage the lungs, heart, skin, nerves and gastrointestinal system. It is potentially fatal and affects roughly 118,000 people worldwide. Fasenra binds to the IL-5 receptor alpha, directly targeting the eosinophils. Published evidence suggests there is a "very rapid and near depletion of both blood and tissue eosinophils as a result of this mechanism of action," Menzies-Gow said. The drug won its original approval in SEA back in 2017. It didn’t take Fasenra long to achieve blockbuster status, as the drug generated sales of $1.26 billion in 2021. But sustaining the growth rate has been difficult without gaining another indication. Last year, Fasenra sales increased (PDF) by 11% to $1.4 billion, compared to $1.86 billion for Nucala.

DUBLIN, July 14, 2023 /PRNewswire/ -- The "Chronic Obstructive Pulmonary Disease - Pipeline Insight, 2023" clinical trials has been added to ResearchAndMarkets.com's offering. With an extensive focus on 65+ companies and 70+ pipeline drugs, this report provides a detailed analysis of the current scenario and growth prospects across the indication. The report encompasses a comprehensive overview of the pipeline drug profiles, covering both clinical and nonclinical stage products. Additionally, it includes a thorough assessment of therapeutics, considering product type, stage, route of administration, and molecule type. Inactive pipeline products in this space are also highlighted, providing a holistic view of the COPD pipeline landscape. To provide a comprehensive understanding, this report outlines the present scenario and growth prospects in the COPD field. It offers detailed insights into the disease overview and treatment guidelines for Chronic Obstructive Pulmonary Disease, setting the stage for a deeper exploration of the pipeline landscape. Furthermore, the report delves into the commercial assessment and clinical assessment of the pipeline products under development. It provides detailed descriptions of each drug, including their mechanisms of action, clinical studies, NDA approvals (if any), and comprehensive product development activities. This encompasses technology, COPD collaborations, licensing, mergers and acquisitions, funding, designations, and other relevant product-related details. Report Highlights The companies and academics are working to assess challenges and seek opportunities that could influence Chronic Obstructive Pulmonary Disease R&D. The therapies under development are focused on novel approaches to treat/improve Chronic Obstructive Pulmonary Disease. Chronic Obstructive Pulmonary Disease Emerging Drugs Chapters This segment of the Chronic Obstructive Pulmonary Disease report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Chronic Obstructive Pulmonary Disease Emerging Drugs Benralizumab: AstraZeneca Benralizumab is a humanized recombinant monoclonal antibody of the isotype IgG1k immunoglobulin that specifically binds to the alpha chain of the interleukin-5 receptor (IL-5R) expressed on eosinophils and basophils. It inhibits the binding of IL-5 as well as the hetero-oligomerization of the alpha and beta subunits of the IL-5R, thus blocking, signal transduction. Dupilumab: Sanofi Dupilumab is a fully human monoclonal antibody of the immunoglobulin G4 subclass that binds to the interleukin-4 (IL-4) receptor, inhibiting the receptor signaling pathways. As an interleukin-4 receptor alpha antagonist, dupilumab inhibits the signaling of pro-inflammatory cytokines, called interleukins (IL) that induce inflammatory and immunological reactions in several atopic or allergic conditions, such as eczema, allergic reactions, and rhinosinusitis. Dupilumab was generated by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture. Dupilumab is under investigation for its potential therapeutic use in chronic obstructive pulmonary disease and is currently in the Phase III stage of development. Tezepelumab: Amgen Tezepelumab (Tezspire) is a first-in-class human monoclonal antibody that works on the primary source of inflammation: the airway epithelium, which is the first point of contact for viruses, allergens, pollutants, and other environmental insults. Specifically, TEZSPIRE targets and blocks TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and initiates an overreactive immune response to allergic, eosinophilic, and other types of airway inflammation associated with severe asthma. TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses, and other airborne particles. Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity. Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control. Tezspire is being developed in collaboration with AstraZeneca and is currently being evaluated in Phase II to treat patients with chronic obstructive pulmonary disease. SNG001: Synairgen SNG001 boosts antiviral responses in the lungs, has a beneficial effect on lung function, and in more difficult to treat patients, improves asthma control during cold infections. The drug is currently being evaluated in the Phase II stage of development to treat patients with COPD. GSK3923868: GlaxoSmithKline GSK3923868, is a PI4kb inhibitor in development as a treatment for viral COPD exacerbations. It belongs to the class of antiasthmatics. The drug acts as a 1-phosphatidylinositol-4-kinase inhibitor. Currently, the drug is in Phase I of its clinical trial evaluation for the treatment of chronic obstructive pulmonary disease. Chronic Obstructive Pulmonary Disease: Therapeutic Assessment This segment of the report provides insights about the different Chronic Obstructive Pulmonary Disease drugs segregated based on following parameters that define the scope of the report, such as: Major Players in Chronic Obstructive Pulmonary Disease There are approx. 65+ key companies which are developing the therapies for Chronic Obstructive Pulmonary Disease. The companies which have their Chronic Obstructive Pulmonary Disease drug candidates in the most advanced stage, i.e. phase III include, AstraZeneca. Phases Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Products have been categorized under various ROAs such as Oral Intravenous Subcutaneous Intramuscular Molecule Type Products have been categorized under various Molecule types such as Recombinant fusion proteins Small molecule Monoclonal antibody Peptide Product Type Chronic Obstructive Pulmonary Disease Report Insights Chronic Obstructive Pulmonary Disease Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs Key Players Sanofi AstraZeneca Amgen Synairgen GlaxoSmithKline Eisai Meridigen Biotech Chiesi EmeraMed Limited Verona Pharma Tetherex Pharmaceuticals Mereo BioPharma Key Products Lemborexant UMC119-06 CHF5259 Emeramide Ensifentrine SNG001 GSK3923868 Benralizumab Dupilumab Tezepelumab SelK2 BCT197 For more information about this clinical trials report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. 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