Pulmonary Eosinophilia

ROCKVILLE, Md. and SUZHOU, China, Feb. 29, 2024 /PRNewswire/ -- Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, announces that the first participant has been dosed in Australia in a first-in-human (FIH) phase 1 clinical trial of IBI3002, a global first-in-class bispecific antibody targeting Interleukin 4 receptor α (IL-4Rα) and thymic stromal lymphopoietin (TSLP). This FIH study (NCT06213844) is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) (only in participants with asthma) of IBI3002 in healthy participants and participants with mild to moderate asthma, and to support further global clinical development of IBI3002. IBI3002 is a humanized bispecific antibody targeting cell surface IL-4Rα and the alarmin cytokine TSLP, discovered and developed by Innovent for the treatment of inflammatory diseases, including asthma. IL-4 receptors mediate the IL-4 signaling (both type 1 and type 2) and the IL-13 signaling (type 2). Both cytokine signaling pathways play key roles in the pathophysiology of type 2 (T2) inflammatory disorders1. TSLP is an epithelial cell-derived alarmin cytokine and triggers both T2 and non-T2 inflammation in asthma2. IBI3002 has high-efficient dual-blocking function on both IL-4Rα and TSLP. In-vitro assays have shown superiority over the marketed monoclonal antibodies to respective target. By targeting both IL-4Rα and TSLP, IBI3002 is hypothesized to have potential effect in suppressing T2 and non-T2 inflammation. The potential synergistic effect in suppressing T2 inflammation is believed to be the basis of its superior efficacy in the treatment of T2 inflammatory disorders. Dr. Lei Qian, Vice President of Clinical Development at Innovent, stated, "In the last few decades, knowledge about both pathophysiological mechanisms, clinical phenotypes and therapeutic options for asthma have significantly increased. In particular, the introduction of biologics for severe asthma paved the way to a true revolution in the field of asthma management, by potentially allowing a precision medicine approach. Targeting specific steps of the immune-inflammatory cascade through highly selective drugs represents a true revolution in the field of severe asthma management, and brings with it the potential of achieving optimal disease control in different severe asthma inflammatory phenotypes. We are looking forward to the development of this molecule in asthma and other inflammatory diseases." About Asthma Asthma is a heterogeneous disease driven by multiple immune cells, cytokines and inflammatory mediators, affecting all age groups. Characterized by variable symptoms of wheeze, shortness of breath, cough, and chest tightness, asthma is associated with chronic airway inflammation, reversible airflow limitation, and airway hyperresponsiveness3. According to the 2015 Global Burden of Disease (GBD) study, about 358 million people are suffering from asthma4. Asthma can be broadly classified as eosinophilic or non-eosinophilic on the basis of airway or peripheral blood cellular profiles. Eosinophilic inflammation is driven predominantly by T2 inflammation, including T-helper cells type 2 and group 2 innate lymphoid cells5. Compared with eosinophilic asthma, non-eosinophilic asthma is poorly understood6. Up to 10% of adults and 2.5% of children with asthma have severe asthma7. Patients with severe asthma have persistent symptoms or frequent exacerbations that require repetitive systemic glucocorticoid bursts or maintenance, despite adequate treatment with high-dose inhaled treatments8. In these patients, add-on treatment, which may include biologic therapies, is needed to reduce the disease burden2,3. About IBI3002 IBI3002 is a global first-in-class bispecific antibody targeting cell surface IL-4Rα and the alarmin cytokine TSLP. It has high-efficient dual-blocking function on both IL-4Rα and TSLP. In-vitro assays have shown superiority over the marketed monoclonal antibodies to respective targets. By simultaneously targeting IL-4Rα and TSLP, IBI3002 has the potential of treating several inflammatory disorders, including asthma. IL-4 is a central mediator of type 2 lymphocyte cell differentiation; it induces the production of type 2 associated cytokines such as IL-5, IL-9, IL-13, and/or type 2 related chemokines as thymus and activation-regulated chemokine (TARC/CCL17) and eotaxins-3. IL-4 involved in B cells regulated isotype class switching to produce serum IgE, and the eosinophils recruitment through IL-5 releasement. Although IL-13 displays some redundancies in these pro-inflammatory processes, it has additional roles in mediating goblet cell hyperplasia, mucus production, smooth muscle contractility, and airway hyperresponsiveness. Together, IL-4 and IL-13 play critical roles in T2 inflammation1. TSLP is an epithelial cell-derived alarmin cytokine that occupies an upstream position in the T2 inflammation induction and Th2 cells differentiation and maturation via IL-4, IL-5 and IL-13 production. TSLP is also believed to be a trigger of non-T2 inflammation in asthma 2. About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable illnesses. Its pioneering therapies to treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 3 new drug applications under the NMPA review, 4 assets in Phase III or pivotal clinical trials and 20 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit , or follow Innovent on Facebook and LinkedIn. Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s). Forward-looking statement This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent Biologics ("Innovent"), are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond the Company's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, the Company's competitive environment and political, economic, legal and social conditions. The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialise or turn out to be incorrect. References: 1. Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production[J]. Cytokine, 2015, 75(1): 14-24. 2. Brusselle G G, Koppelman G H. Biologic therapies for severe asthma[J]. New England Journal of Medicine, 2022, 386(2): 157-171. 3. Global Initiative for Asthma. 2023 GINA Report, Global Strategy for Asthma Management and Prevention. 2023. 4. GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 [published correction appears in Lancet Respir Med. 2017 Oct;5(10 ):e30]. Lancet Respir Med. 2017;5(9):691-706. 5. Gans MD, Gavrilova T. Understanding the immunology of asthma: Pathophysiology, biomarkers, and treatments for asthma endotypes. Paediatr Respir Rev. 2020;36:118-127. 6. Israel E, Reddel H K. Severe and difficult-to-treat asthma in adults[J]. New England Journal of Medicine, 2017, 377(10): 965-976. 7. Settipane RA, Kreindler JL, Chung Y, Tkacz J. Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4/5 therapy in the United States. Ann Allergy Asthma Immunol 2019; 123(6): 564-572.e3. 8. Caminati M, Vaia R, Furci F, Guarnieri G, Senna G. Uncontrolled Asthma: Unmet Needs in the Management of Patients. J Asthma Allergy. 2021;14:457-466. SOURCE Innovent Biologics

One concern about the GLP-1 class of metabolic disorder drugs is that the weight patients lose includes muscle as well as fat. BioAge Labs wants to test whether its experimental medication, dosed alongside Eli Lilly’s weight management drug Zepbound, can preserve muscle mass. The startup recently closed $170 million to finance a mid-stage clinical trial. BioAge develops drugs that address aspects of human aging. Its lead drug candidate, azelaprag, is a small molecule designed to bind to and activate the apelin receptor, which regulates muscle metabolism, growth, and repair. This drug came from the labs of Amgen, which initially developed it for treating heart failure. Amgen’s Phase 1 tests showed the drug hit its target with a clean safety profile, BioAge CEO Kristen Fortney told MedCity News in a 2022 interview. But as a heart drug, the results were “not dramatic,” she said. Amgen elected to shelve the molecule. Richmond, California-based BioAge licensed it from the pharma giant in 2021, with the goal of testing it as a way of preserving muscle mass in elderly people. In BioAge’s Phase 1b study enrolling 21 participants age 65 and older, results showed the experimental drug led to statistically significant prevention of muscle atrophy relative to a placebo after 10 days of bed rest. The company planned to proceed to larger Phase 2 test enrolling intensive care unit patients, who can lose more than 15% of their muscle mass in just one week, according to published research. Last fall, BioAge announced the Phase 2 trial would go in a different direction. Instead of testing azelaprag in ICU patients, the trial will evaluate the drug alongside Eli Lilly’s Zepbound. The injectable drug, which activates the GLP-1 and GIP receptors, is an incretin mimetic, a type of drug that works by mimicking hormones found in the gut. The new clinical trial plan is based on preclinical research in obese mice. Results reported last year showed that treating the mice with both azelaprag and Lilly’s drug led to greater weight loss than what was achieved with the Lilly drug alone. The drug pairing also led to improvement in body composition and muscle function. Under a collaboration agreement, Lilly will supply Zepbound for BioAge’s trial, which will be run in collaboration with Chorus, a small independent clinical development organization within the pharma giant. BioAge adjusted its focus for azelaprag after the company’s technology uncovered new insight about the molecule. The BioAge discovery platform, built on analysis of human longevity data, identified a link between the apelin pathway activity and physical function during aging, Fortney said in an email. While the Phase 1b clinical trial led to results showing significant muscle and metabolic benefits in healthy elderly volunteers on bed rest, the molecule’s mechanism has multiple potential applications, Fortney said. “Obesity is the indication we are focusing on given the strong weight loss synergy we see preclinically with incretins,” she said. “This is an oral drug with the potential to increase weight loss quantity with a fully oral regimen, as well as to improve weight loss quality.” Fortney said BioAge will share more details on the design of the Phase 2 trial in the future, but the study will compare azelaprag (known at BioAge as BGE-105) in combination with Zepbound versus Zepbound alone. The primary endpoint will be weight loss. In addition, the company will monitor exploratory endpoints related to improvement of body composition—the balance of lean mass to fat mass. BioAge’s new capital will finance the planned Phase 2 test, which is on track to start in mid-2024. The Series D round was led by Sofinnova Investments. New investors joining the financing include Longitude Capital, RA Capital Management, Cormorant Asset Management, RTW Investments, SV Health Investors, OrbiMed Advisors, Sands Capital, Pivotal bioVenture Partners, Osage University Partners, Lilly Ventures, and Amgen Ventures. The latest round also included participation from earlier investor Andreessen Horowitz. Here’s a look at other recent life science industry financing activity: —Frontier Medicines, developer of targeted medicines for oncology and immunology, closed $80 million in financing to support its pipeline. The biotech’s most advanced program is FMC-376, which is in development for treating patients whose cancer is positive for KRAS G12C. This mutation was first drugged by Lumakras from Amgen and then Krazati from Mirati Therapeutics. Both drugs lock KRAS G12C protein in an inactive state. Frontier’s drug candidate is designed to block this cancer-driving protein in either its active or inactive states, potentially offering an option for patients who have not responded to the Amgen or Mirati drugs. In addition to supporting FMC-376, which recently dosed the first patient in a Phase 1/2 study, Frontier said the new capital will support other wholly owned programs in its pipeline. Deerfield Management Company and Droia Venture co-led the company’s Series C financing, which also included “significant participation” by Belgium-based drugmaker Galapagos. Frontier last raised money in 2021, an $88.5 million Series B round. —Firefly Bio revealed $94 million to finance R&D of degrader antibody conjugates, or DACs, which carry a protein degrader as the drug payload. In preclinical research, the biotech said its drugs led to “significant reduction of tumor volume at very low doses.” Firefly was incubated by Versant Ventures, which co-led the startup’s Series A financing with MPM BioImpact. —Roche, already an investor in liquid biopsy company Freenome, led an additional $254 million financing for the company. South San Francisco-based Freenome will apply the cash toward ongoing pivotal clinical trials evaluating its blood screening technology in colorectal cancer and lung cancer. The company is also conducting a study of its technology as a way to detect multiple cancers. Roche last invested in Freenome two years ago, a $290 million infusion that followed the company’s $300 million Series D financing. —Latigo Biotherapeutics launched with $135 million to finance clinical development of a non-opioid drug that blocks NaV1.8, a sodium channel associated with pain. It’s the same target addressed by a Vertex Pharmaceuticals drug candidate that recently posted data showing it met its main Phase 3 goal assessing pain relief compared to a placebo. But on a secondary goal of showing superiority to standard of care Vicodin, the Vertex drug came up short. Thousand Oaks, California-based Latigo claims its drug could be best in the class of NaV1.8 inhibitors with rapid onset, meaningful efficacy, and superior safety. It’s currently in Phase 1 testing. Latigo’s Series A financing was led by Westlake Village BioPartners, which incubated the startup. —Cancer immunotherapy developer NextPoint Therapeutics added $42.5 million to its Series B financing, bringing the round’s total to $122.5 million. The drugs of Cambridge, Massachusetts-based NextPoint target the HHLA2 pathway. NextPoint first announced its Series B round last year. —Sudo Biosciences expanded its Series B financing by $31 million, bringing the round’s total to $147 million. The new investors are Dementia Discovery Fund, Leaps by Bayer, and UPMC Enterprises. Carmel, Indiana-based Sudo emerged from stealth in 2022 to develop small molecule drugs that address TYK2, an autoimmune disease target first hit by the Bristol Myers Squibb drug Sotyktu. —Alys Pharmaceuticals launched with $100 million from Medicxi, the investment firm that formed the company. The preclinical biotech, which focuses on developing treatments for immune disorders of the skin, was formed by combining six Medicxi portfolio companies. Target indications include atopic dermatitis, vitiligo, psoriasis, and mastocytosis. —Antibody drug conjugate developer ProfoundBio closed $112 million in financing, which will be applied to clinical development of its pipeline. Lead program rinatbart sesuctecan, or Rina-S, targets folate receptor alpha, a validated cancer target. A pivotal Phase 1/2 study is underway in ovarian cancer. Ally Bridge Group led the Seattle-based biotech’s Series B round. ProfoundBio, whose management team brings experience from ADC specialist Seagen, emerged in 2021 backed by a $55 million Series A financing. —Areteia Therapeutics expanded its Series A round by $75 million with the addition of new investors Viking Global Investors and Marshall Wace. The Chapel Hill, North Carolina-based biotech’s Series A financing was announced at $350 million in 2022. Lead drug candidate dexpramipexole comes from the labs of Knopp Biosciences. Areteia is currently testing the molecule in three Phase 3 clinical trials enrolling patients with eosinophilic asthma, a severe form of asthma. —Basking Biosciences raised $55 million in a financing led by Arch Venture Partners. Columbus, Ohio-based Basking will use the capital to continue clinical development of BB-031, a potential treatment for acute ischemic stroke. The Basking drug is a reversible RNA aptamer designed to target von Willebrand factor, a clotting protein. BB-031 is engineered for both rapid onset and short duration of effect. Basking plans to start Phase 2 testing later this year. —Neurona Therapeutics, developer of regenerative medicines for neurological disorders, closed $120 million in financing. The San Francisco-based biotech makes cell therapies from human pluripotent stem cells, which have the ability to become almost any type of cell. Neurona will apply the capital toward ongoing Phase 1/2 testing of NRTX-1001, developed as a one-time treatment to silence epileptic seizures. Viking Global Investors and Cormorant Asset Management co-led Neurona’s Series E round. —Cour Pharmaceuticals has already out-licensed a celiac disease therapeutic candidate to Takeda Pharmaceuticals, which has advanced the nanoparticle-based therapy to Phase 2 testing. Chicago-based Cour wants to develop its own drug candidates and it raised $105 million to support programs in type 1 diabetes and myasthenia gravis. Lumira Ventures and Alpha Wave Ventures co-led the Series A financing, which included participation from three big pharma companies. —Eyconis, a new company formed with assets from Ascendis Pharma, launched with a $150 million financing commitment from an investor syndicate that includes Frazier Life Sciences, RA Capital Management, venBio, and HealthQuest Capital. Eyconis, which will operate from Redwood City, California, has ophthalmology assets developed from Ascendis’s Transcon platform. Ascendis, which has an equity stake in Eyconis, granted the biotech rights to develop and commercialize Transcon ophthalmology products globally. —Synnovation Therapeutics, founded and led by veterans of Incyte, launched with $102 million for small molecule drugs addressing validated cancer targets. Lead program SNV1521 is a PARP1 inhibitor that is highly selective to that target and also has the ability to penetrate into the central nervous system. The Wilmington, Delaware-based company is testing this molecule in a Phase 1 clinical trial. Third Rock Ventures led Synnovation’s Series A financing, which included participation from Nextech, Lilly Asia Ventures, Sirona Capital, and Cormorant Asset Management. Photo by Eli Lilly

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