Tozorakimab

New data for TEZSPIRE and BREZTRI demonstrate AstraZeneca’s innovation and commitment to transform care in COPD WILMINGTON, Del.--(BUSINESS WIRE)-- AstraZeneca will showcase new clinical and real-world data across its leading inhaled, biologic and early science respiratory portfolio at the American Thoracic Society (ATS) International Conference, in San Diego, CA from May 17 - 22, 2024. The company will present 59 abstracts, including 12 late-breaking posters, with a focus on unmet needs in chronic obstructive pulmonary disease (COPD), severe asthma and eosinophilic granulomatosis with polyangiitis (EGPA), as well as other chronic respiratory diseases. Sharon Barr, Ph.D., Executive Vice President, BioPharmaceuticals R&D, AstraZeneca said: “Data at ATS demonstrate our progress in advancing a new wave of innovative treatments, moving beyond symptom control into disease modification, remission and one day, cure. Today, COPD patients have highly limited options if their disease is uncontrolled on inhaled medicines. We’re encouraged by the results of the COURSE Phase IIa data exploring tezepelumab in a broad population of COPD patients beyond those with baseline blood eosinophils above 300 cells/μL and look forward to these data being presented at the ATS International Conference.” Ruud Dobber, Ph.D, Executive Vice President and President, BioPharmaceuticals Business Unit, AstraZeneca, said: “Our broad pipeline and portfolio of inhaled and biologic medicines are the cornerstone of our bold ambition to transform respiratory care. COPD remains one of the leading causes of death globally, and at ATS we will present important real-world evidence reinforcing the need to address cardiopulmonary risk in COPD as well as the potential for our inhaled triple therapy BREZTRI to reduce this risk.” Highlights of AstraZeneca data at ATS 2024 include: Leading transformation in COPD care by investigating novel biologic medicines, targeting key drivers across a broad range of patients including: TEZSPIRE® (tezepelumab) beyond severe asthma targeting thymic stromal lymphopoietin (TSLP) and tozorakimab, to reduce excess inflammation and epithelial remodelling in IL-33 driven disease COURSE Phase IIa trial: late-breaking data from a proof-of-concept trial investigating tezepelumab in moderate to very severe COPD patients. Importantly this trial included COPD patients irrespective of inflammatory drivers, baseline blood eosinophil levels, emphysema, chronic bronchitis, and smoking status.1 New mechanistic data from tozorakimab investigating its ability to inhibit IL-33ox biologic effects and block the RAGE-EGFR pathway vs. other IL-33 antibodies.2 Investigating the effect of inhaled triple therapy, BREZTRI® (budesonide/ glycopyrrolate/ formoterol fumarate, BGF), on cardiopulmonary outcomes and deepening insights into the connection between COPD and cardiopulmonary risk ETHOS Phase III trial post-hoc analysis of cardiopulmonary outcomes: the new analysis explores the effect of BGF across a range of cardiopulmonary outcomes beyond traditional COPD endpoints.3 SKOPOS-MAZI retrospective analysis: the study will provide new real-world evidence comparing mortality rates in patients who start therapy with BGF single inhaler triple therapy (SITT), versus multiple inhaler triple therapy (MITT) [open combination triple therapies (ICS/LABA+ LAMA or LABA/LAMA + ICS)] among patients with COPD in the US.4 EXACOS-CV multi-country retrospective cohort study: late-breaking real-world data across 8 countries, from over 1 million patients with COPD explores the risk of serious cardiovascular events or death following a COPD exacerbation. These data add to the growing body of evidence demonstrating the importance of proactively addressing cardiopulmonary risk in COPD patients.5 In asthma, advancing the science in asthma rescue with AIRSUPRA® (albuterol-budesonide), a first-in-class anti-inflammatory rescue therapy for asthma in the US6 MANDALA Phase III post-hoc analysis: new efficacy data for as-needed AIRSUPRA by baseline blood eosinophil count in patients with moderate-to-severe asthma.7 ACADIA trial design: outlining innovative approaches to study design for the ACADIA study of AIRSUPRA in adolescents.8 Early pipeline science exploring innovative modalities including novel inhaled medicines for moderate-severe add-on treatment (“pre-biologics”) to reach a broader population of patients Two potential first-in-class pre-biologic medicines being explored in asthma: New Phase I safety and efficacy data for AZD8630/AMG 104, an inhaled TSLP inhibitor in patients with moderate-to-severe asthma.9 Findings from a preclinical study of AZD4604, an inhaled, small molecule selective JAK1 inhibitor in development for the treatment of moderate-to-severe asthma. The data explores JAK selectivity and implications for clinical inhibition compared to other currently marketed JAK inhibitors.10 Additional AstraZeneca presentations of note include results from the MANDARA Phase III trial for patients with EGPA. A highlight of the MANDARA data is the impact of FASENRA® (benralizumab) to reduce or completely eliminate oral glucocorticoid use in these patients.11 Key AstraZeneca presentations during ATS 2024: Presenting author Abstract title Presentation details TEZSPIRE (tezepelumab) Singh D Tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD): efficacy and safety from the Phase 2a COURSE study 705 Poster Session A101 Sunday, May 19 2:15 PM – 4:15 PM Singh D Tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD): efficacy and safety from the Phase 2a COURSE study Late Breaking Mini Symposium Session B13 Ballroom 20A Monday, May 20 9:15 AM – 11:15 AM Lugogo N A Phase 4, single-arm, open-label study to evaluate the effectiveness and safety of tezepelumab in patients with severe asthma, including under-represented groups – Initial results of the PASSAGE study P646 Thematic Poster Session C34 Tuesday, May 21 9:15 AM – 4:15 PM Lugogo N Clinical responses to tezepelumab in patients with severe, uncontrolled asthma and history of nasal polyps from the NAVIGATOR study P595 Thematic Poster Session C31 Tuesday, May 21 9:15 AM – 4:15 PM BREZTRI AEROSPHERE (budesonide/glycopyrrolate/formoterol fumarate) Singh D Effect of triple inhaled therapy with budesonide/glycopyrrolate/formoterol fumarate on cardiopulmonary events in chronic obstructive pulmonary disease: a post-hoc analysis of ETHOS 913 Poster discussion A27 Sunday, May 19 9:15 AM – 11:15 AM Marshall J In silico lung deposition profiles of three single-inhaler triple therapy combinations assessed with functional respiratory imaging (FRI) at a low inspiratory flow rate 919 Poster discussion A27 Sunday, May 19 9:15 AM – 11:15 AM Pollack M Association between severe cardiovascular events and time following exacerbations of COPD: meta-analyses of EXACOS-CV observational studies from 8 countries P159 Thematic Poster Session A48 Sunday, May 19 11:30 AM – 1:15 PM Pollack M Reduced risk of mortality for COPD patients associated with initiation of treatment with single inhaler (budesonide/glycopyrrolate/formoterol) versus multiple inhaler triple therapy in the United States: the MAZI study P626 Thematic Poster Session B52 Monday, May 20 11:30 AM – 1:15 PM FASENRA (benralizumab) Jackson D Systematic literature review of real-world outcomes of benralizumab in eosinophilic granulomatosis with polyangiitis P655 Thematic Poster Session C34 Tuesday, May 21 11:30 AM – 1:15 PM Pitrez PM Impact of disease, use of biologics and clinical remission in severe asthma: insights from a multicenter longitudinal real-life registry in Brazil P638 Thematic Poster Session C34 Tuesday, May 21 11:30 AM – 1:15 PM Nair P Effect of benralizumab versus mepolizumab on reduction in oral glucocorticoid use in patients with eosinophilic granulomatosis with polyangiitis: Phase 3 MANDARA study 314 RAPiD Poster Discussion Session C102 Tuesday, May 21 2:15 PM – 4:15 PM AIRSUPRA (albuterol/budesonide) Papi A Efficacy of as-needed albuterol-budesonide by baseline blood eosinophil count in patients greater than or equal to 18 years with moderate-to-severe asthma P604 Thematic Poster Session C31 Tuesday, May 21 11:30 AM – 1:15 PM Bacharier LB A Bayesian Dynamic Borrowing Approach to Evaluate the Efficacy of Albuterol-Budesonide As Needed in Adolescents with Asthma: Design of the ACADIA Study P616 Thematic Poster Session C31 Tuesday, May 21 11:30 AM – 1:15 PM Asthma Lanz M Comparative burden of disease associated with short-acting beta2-agonist and systemic corticosteroid exposures in US children, adolescents, and adults with asthma 302 RAPiD Poster Discussion C102 Tuesday, May 21 2:15 PM – 4:15 PM Early Respiratory & Immunology Doffman S Phase 1 safety and efficacy of AZD8630/AMG 104 inhaled anti-TSLP in healthy volunteers and patients with asthma on medium-high dose inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) with elevated baseline fractional exhaled nitric oxide (FeNO) P406 Thematic Poster Session A34 Sunday, May 19 11:30 AM – 1:15 PM Riff C Inhaled AZD4604: local Janus Kinase 1 inhibition without systemic activity P297 Thematic Poster Session B71 Monday, May 19 9:15 AM – 4:15 PM Cohen ES Distinct pharmacology profiles of IL-33 antibodies P594 Thematic Poster Session B32 Monday, May 20 9:15 AM – 4:15 PM Ritchie AI Structural predictors of lung function decline in the British Early COPD Network (BEACON) cohort Mini Symposium Session C99 Tuesday, May 21 2:15 PM – 4:15 PM Respiratory Sustainability Shah M Systemic exposure bioequivalence of budesonide/glycopyrrolate/formoterol fumarate with the potential next generation propellant hydrofluoroolefin-1234ze versus hydrofluoroalkane-134a in healthy adults P628 Thematic Poster Session B52 Monday, May 21 11:30 AM – 1:15 PM Bell JP EXACOS CARBON: describing the greenhouse gas emissions of healthcare resource utilization by frequency and severity of COPD exacerbation in England P192 Thematic Poster Session A54 Sunday, May 19 11:30 AM – 1:15 PM INDICATIONS AND LIMITATIONS OF USE / ISI AIRSUPRA® (albuterol and budesonide) Contraindications: Hypersensitivity to albuterol, budesonide, or to any of the excipients Deterioration of Asthma: Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient continues to experience symptoms after using AIRSUPRA or requires more doses of AIRSUPRA than usual, it may be a marker of destabilization of asthma and requires evaluation of the patient and their treatment regimen Paradoxical Bronchospasm: AIRSUPRA can produce paradoxical bronchospasm, which may be life threatening. Discontinue AIRSUPRA immediately and institute alternative therapy if paradoxical bronchospasm occurs. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister Cardiovascular Effects: AIRSUPRA, like other drugs containing beta2-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients, as measured by pulse rate, blood pressure, and/or other symptoms. If such effects occur, AIRSUPRA may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST-segment depression. Therefore, AIRSUPRA, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension Do Not Exceed Recommended Dose: Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs Hypersensitivity Reactions, Including Anaphylaxis: Can occur after administration of albuterol sulfate and budesonide, components of AIRSUPRA, as demonstrated by cases of anaphylaxis, angioedema, bronchospasm, oropharyngeal edema, rash, and urticaria. Discontinue AIRSUPRA if such reactions occur Risk of Sympathomimetic Amines with Certain Coexisting Conditions: AIRSUPRA, like all therapies containing sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines Hypokalemia: Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients. The decrease in serum potassium is usually transient, not requiring supplementation Immunosuppression and Risk of Infections: Due to possible immunosuppression from the use of inhaled corticosteroids (ICS), potential worsening of infections could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients Oropharyngeal Candidiasis: Has occurred in patients treated with ICS agents. Monitor patients periodically. Advise patients to rinse his/her mouth with water, if available, without swallowing after inhalation Hypercorticism and Adrenal Suppression: May occur with very high doses in susceptible individuals. If such changes occur, consider appropriate therapy Reduction in Bone Mineral Density: Decreases in bone mineral density have been observed with long-term administration of ICS. For patients at high risk for decreased bone mineral density, assess initially and periodically thereafter Glaucoma and Cataracts: Have been reported following the long-term administration of ICS, including budesonide, a component of AIRSUPRA Effects on Growth: Orally inhaled corticosteroids, including budesonide, may cause a reduction in growth velocity when administered to pediatric patients. The safety and effectiveness of AIRSUPRA have not been established in pediatric patients, and AIRSUPRA is not indicated for use in this population Most common adverse reactions (incidence ≥ 1%) are headache, oral candidiasis, cough, and dysphonia Drug Interactions: AIRSUPRA should be administered with caution to patients being treated with: Strong cytochrome P450 3A4 inhibitors (may cause systemic corticosteroid effects) Short-acting bronchodilators (concomitant use of additional beta-agonists with AIRSUPRA should be used judiciously to prevent beta-agonist overdose) Beta-blockers (may block pulmonary effects of beta-agonists and produce severe bronchospasm) Diuretics or non-potassium-sparing diuretics (may potentiate hypokalemia or ECG changes). Consider monitoring potassium levels Digoxin (may decrease serum digoxin levels). Consider monitoring digoxin levels Monoamine oxidase inhibitors (MAOI) or tricyclic antidepressants (Use AIRSUPRA with extreme caution; may potentiate effect of albuterol on the cardiovascular system) Use AIRSUPRA with caution in patients with hepatic impairment, as budesonide systemic exposure may increase. Monitor patients with hepatic disease INDICATION AIRSUPRA is a combination of albuterol, a beta2-adrenergic agonist and budesonide, a corticosteroid, indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma 18 years of age and older. Please see full Prescribing Information, including Patient Information. You may report side effects related to AstraZeneca products. BREZTRI AEROSPHERE® (budesonide, glycopyrrolate, and formoterol fumarate) Inhalation Aerosol BREZTRI is contraindicated in patients who have a hypersensitivity to budesonide, glycopyrrolate, formoterol fumarate, or product excipients BREZTRI is not indicated for treatment of asthma. Long-acting beta2-adrenergic agonist (LABA) monotherapy for asthma is associated with an increased risk of asthma-related death. These findings are considered a class effect of LABA monotherapy. When a LABA is used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone. Available data do not suggest an increased risk of death with use of LABA in patients with COPD BREZTRI should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition BREZTRI is NOT a rescue inhaler. Do NOT use to relieve acute symptoms; treat with an inhaled short-acting beta2-agonist BREZTRI should not be used more often than recommended; at higher doses than recommended; or in combination with LABA-containing medicines, due to risk of overdose. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs Oropharyngeal candidiasis has occurred in patients treated with orally inhaled drug products containing budesonide. Advise patients to rinse their mouths with water without swallowing after inhalation Lower respiratory tract infections, including pneumonia, have been reported following ICS. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap Due to possible immunosuppression, potential worsening of infections could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients Particular care is needed for patients transferred from systemic corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients during and after transfer. Taper patients slowly from systemic corticosteroids if transferring to BREZTRI Hypercorticism and adrenal suppression may occur with regular or very high dosage in susceptible individuals. If such changes occur, consider appropriate therapy Caution should be exercised when considering the coadministration of BREZTRI with long-term ketoconazole and other known strong CYP3A4 Inhibitors. Adverse effects related to increased systemic exposure to budesonide may occur If paradoxical bronchospasm occurs, discontinue BREZTRI immediately and institute alternative therapy Anaphylaxis and other hypersensitivity reactions (eg, angioedema, urticaria or rash) have been reported. Discontinue and consider alternative therapy Use caution in patients with cardiovascular disorders, especially coronary insufficiency, as formoterol fumarate can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles Decreases in bone mineral density have been observed with long-term administration of ICS. Assess initially and periodically thereafter in patients at high risk for decreased bone mineral content Glaucoma and cataracts may occur with long-term use of ICS. Worsening of narrow-angle glaucoma may occur, so use with caution. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use BREZTRI long term. Instruct patients to contact a healthcare provider immediately if symptoms occur Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if symptoms occur Use caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis or unusually responsive to sympathomimetic amines Be alert to hypokalemia or hyperglycemia Most common adverse reactions in a 52-week trial (incidence ≥ 2%) were upper respiratory tract infection (5.7%), pneumonia (4.6%), back pain (3.1%), oral candidiasis (3.0%), influenza (2.9%), muscle spasms (2.8%), urinary tract infection (2.7%), cough (2.7%), sinusitis (2.6%), and diarrhea (2.1%). In a 24-week trial, adverse reactions (incidence ≥ 2%) were dysphonia (3.3%) and muscle spasms (3.3%) BREZTRI should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors and tricyclic antidepressants, as these may potentiate the effect of formoterol fumarate on the cardiovascular system BREZTRI should be administered with caution to patients being treated with: Strong cytochrome P450 3A4 inhibitors (may cause systemic corticosteroid effects) Adrenergic drugs (may potentiate effects of formoterol fumarate) Xanthine derivatives, steroids, or non-potassium sparing diuretics (may potentiate hypokalemia and/or ECG changes) Beta-blockers (may block bronchodilatory effects of beta-agonists and produce severe bronchospasm) Anticholinergic-containing drugs (may interact additively). Avoid use with BREZTRI Use BREZTRI with caution in patients with hepatic impairment, as budesonide and formoterol fumarate systemic exposure may increase. Patients with severe hepatic disease should be closely monitored INDICATION BREZTRI AEROSPHERE is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). LIMITATIONS OF USE Not indicated for the relief of acute bronchospasm or for the treatment of asthma. Please see full BREZTRI Prescribing Information, including Patient Information. You may report side effects related to AstraZeneca products. FASENRA ® (benralizumab) CONTRAINDICATIONS Known hypersensitivity to benralizumab or excipients. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions (e.g., 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 (i.e., 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 (e.g., 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 6 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. TEZSPIRE® (tezepelumab) 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. 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. Please see full Prescribing Information, including Patient Information and Instructions for Use. You may report side effects related to AstraZeneca products. Notes Data presented does not reflect any head-to-head comparisons. Chronic Obstructive Pulmonary Disease (COPD) COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems.12 COPD is the third leading cause of death due to chronic disease and the sixth leading cause of mortality in the United States. COPD accounts for the majority of chronic lower respiratory mortality in the US at 150,000 deaths per year, and data suggests patients with COPD are, on average, 50 times more likely to die from their condition compared to those with asthma. 13,14 The lungs and heart are fundamentally linked and work together.15 COPD mechanisms elevate the risk of both lung and heart events, including severe or even fatal COPD exacerbations and cardiac events, known as cardiopulmonary risk.16-19 Approximately 1 in 5 patients with COPD will die within a year of their first hospitalisation for an exacerbation, and pulmonary and cardiac events are a key driver of mortality and the most common reasons for death in patients with COPD.16,20-22 Severe asthma Severe asthma is an often-debilitating, potentially fatal condition affecting up to 26 million people worldwide.23-26 Patients may be uncontrolled despite high dosages of standard of care asthma controller medicines, experiencing frequent exacerbations and significant limitations on lung function and health-related quality of life as a result.23,25-27 Eosinophilic granulomatosis with polyangiitis (EGPA) 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.28,29 It is estimated that 118,000 people throughout the world live with EGPA.30 EGPA can result in damage to multiple organs, including lungs, upper airway, skin, heart, gastrointestinal tract and nerves.28 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. Without treatment, the disease may be fatal.28,31 Almost half (47%) of patients do not achieve remission with current treatments.28,32 AIRSUPRA AIRSUPRA (albuterol/budesonide), formerly known as PT027, is a first-in-class SABA/ICS rescue treatment for asthma in the US, to be taken as needed. It is an inhaled, fixed-dose combination rescue medication containing albuterol (also known as salbutamol), a SABA, and budesonide, a corticosteroid, and has been developed in a pMDI using AstraZeneca’s Aerosphere delivery technology.33 The FDA approval of AIRSUPRA was based on MANDALA and DENALI Phase III trials (Approval press release). In MANDALA, AIRSUPRA significantly reduced the risk of severe exacerbations compared to albuterol in patients with moderate-to-severe asthma when used as an as-needed rescue medication in response to symptoms. For patients treated with AIRSUPRA 180 mcg/160 mcg the annualized total systemic corticosteroids dose when compared with albuterol 180 mcg was statistically significantly different, with a reduction in mean annualized dose of 40 mg per patient. In DENALI, AIRSUPRA significantly improved lung function compared to the individual components albuterol and budesonide in patients with mild to moderate asthma. BREZTRI BREZTRI AEROSPHERE (budesonide/glycopyrronium/formoterol fumarate) is a single-inhaler, fixed-dose triple-combination of formoterol fumarate, a LABA, glycopyrronium bromide, a LAMA, with budesonide, an ICS, and delivered via the AEROSPHERE pressurised metered-dose inhaler. BREZTRI AEROSPHERE is approved to treat COPD in more than 50 countries worldwide including the US, EU, China and Japan, and is currently being studied in Phase III trials for asthma. 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).34,35 FASENRA (benralizumab) is currently approved in more than 80 countries, including the US, EU, and Japan, and is approved for self-administration in the US, EU and other countries.36-38 FASENRA has been prescribed to over 100,000 patients in the US.39 FASENRA is in development for other diseases including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome.40-42 FASENRA was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan. 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.44,45 TEZSPIRE is approved in the US, EU, Japan and other countries for the treatment of severe asthma.46-48 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. In addition, we are also collaborating with AstraZeneca on AMG104/AZD8630, an inhaled anti-TSLP compound currently in development for asthma. In November 2021, Amgen and AstraZeneca agreed to include AMG 104 / AZD8630 in the existing collaboration agreement. The companies share both costs and income, with no inventor royalty. AstraZeneca will be the development, manufacturing and commercial lead. AstraZeneca and Amgen will jointly commercialize AMG 104 / AZD8630 in North America, and AstraZeneca will distribute the product and book sales globally, including for the US. Respiratory & Immunology Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca’s main disease areas and is a key growth driver for the Company. AstraZeneca is an established leader in respiratory care with a 50-year heritage. The Company aims to transform the treatment of asthma and COPD by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. The Company’s early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction. With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Company’s growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca’s ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide. About 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 operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit and follow us on social media @AstraZeneca. References Singh D, Bafadhel M, Brightling C, et al. Tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD): efficacy and safety from the Phase 2a COURSE study. [Late breaking Mini Symposium Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May). Cohen ES, Strickson S, Scott IC, et al. Distinct pharmacology profiles of IL-33 antibodies. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May). Singh D, Martinez FJ, Hurst JR, et al. Effect of triple inhaled therapy with budesonide/glycopyrrolate/formoterol fumarate on cardiopulmonary events in chronic obstructive pulmonary disease: a post-hoc analysis of ETHOS. [Poster Discussion]. Presented at the American Thoracic Society International Conference 2024 (17-22 May). Pollack M, Rapsomaniki E, Anzueto A, et al. Increased risk of mortality for COPD patients associated with initiation of treatment with multiple inhaler triple therapy initiation versus single inhaler (budesonide/glycopyrrolate/formoterol) in the United States: the MAZI study. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May). Pollack M, Nordon C, Rhodes K, et al. Association between severe cardiovascular events and time following exacerbations of COPD: meta-analyses of EXACOS-CV observational studies from 8 countries. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May). AstraZeneca. AIRSUPRA® (PT027) approved in the US for asthma. Available at: . [Last accessed: April 2024]. Papi A, Chipps B, Beasley R, et al. Efficacy of as-needed albuterol-budesonide by baseline blood eosinophil count in patients greater than or equal to 18 years with moderate-to-severe asthma. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May). Bacharier LB, Bardsley S, Dunsire L, et al. A Bayesian Dynamic Borrowing Approach to Evaluate the Efficacy of Albuterol-Budesonide As Needed in Adolescents with Asthma: Design of the ACADIA Study. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May). Doffman S, Dosanjh D, Sadiq MW. Phase 1 safety and efficacy of AZD8630/AMG 104 inhaled anti-TSLP in healthy volunteers and patients with asthma on medium-high dose inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) with elevated baseline fractional exhaled nitric oxide (FeNO). [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May). Riff C, Larsson J, Nilsson M, et al. Inhaled AZD4604: local Janus Kinase 1 inhibition without systemic activity. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May). Nair P, Wechsler M, Bourdin A, et al. Effect of benralizumab versus mepolizumab on reduction in oral glucocorticoid use in patients with eosinophilic granulomatosis with polyangiitis: Phase 3 MANDARA study. [RAPiD Poster Discussion Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May). GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2023. [Online]. Available at: . [Last accessed: April 2024]. Centers for Disease Control and Prevention (CDC). Leading Causes of Death. United States: CDC; January 17, 2024, . Accessed April 11, 2024. National Heart, Lung, and Blood Institute (NIH). Learn More Breathe Better: United States: NIH. . Accessed April 11, 2024. American Lung Association. Your Heart and Lungs: The Ultimate Relationship (2023) Available at: . [Last accessed: April 2024]. Ho TW, Tsai YJ, Ruan SY, et al. In-Hospital and One-Year Mortality and Their Predictors in Patients Hospitalized for First-Ever Chronic Obstructive Pulmonary Disease Exacerbations: A Nationwide Population-Based Study. PLOS ONE. 2014; 9 (12): e114866. Donaldson GC et al. Increased risk of myocardial infarction and stroke following exacerbation of COPD. Chest. 2010;137:1091-1097;9-2029. Watz H et al. Spirometric changes during exacerbations of COPD: A post hoc analysis of the WISDOM trial. Respir Res. 2018;19(1):251. Suissa S et al. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67(11):957-963. Lindenauer PK, Dharmarajan K, Qin L, et al. Risk Trajectories of Readmission and Death in the First Year After Hospitalization for Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2018 Apr 15;197(8):1009-1017. García-Sanz MT, Cánive-Gómez JC, Senín-Rial L, et al. One-year and long-term mortality in patients hospitalized for chronic obstructive pulmonary disease. J Thorac Dis. 2017; 9 (3): 636‐645. doi:10.21037/jtd.2017.03.34. Mannino DM et al. Global Initiative on Obstructive Lung Disease (GOLD) classification of lung disease and mortality: findings from the Atherosclerosis Risk in Communities (ARIC) study. Respir Med. 2006;100: pp.115-122. Chung, KF, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb;43(2):343-73. The Global Asthma Network. The Global Asthma Report 2022. Available at: . [Last accessed: April 2024]. Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med. 2005;172:149-60. Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40: 364-372. Peters SP, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med 2006;100(7):1139-51. American Partnership for Eosinophilic Disorders. Eosinophilic Granulomatosis with Polyangiitis (EGPA). Available at: . [Last accessed: April 2024]. Furuta S, Iwamoto T, Nakajima H. Update on eosinophilic granulomatosis with polyangiitis. Allergol Int. 2019;68:430-436. AstraZeneca Data on file. 2022. REF-167820. Baldini C, et al. Clinical Manifestations and Treatment of Churg-Strauss Syndrome. Rheum Dis Clin N Am. 2010;36:527–543. Cottin V, et al. Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg–Strauss). Eur Respir J. 2016;48:1429-1441. Airsupra (albuterol/budesonide) US prescribing information; 2022. 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. Pham TH, et al. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21-29. AstraZeneca news release. Available at: . [Last accessed: April 2024]. AstraZeneca news release. Available at: . [Last accessed: April 2024]. AstraZeneca Annual Report 2023. Available at: . [Last accessed: April 2024]. AstraZeneca plc. FY and Q4 2023 Results. Conference call and webcast for investors and analysts. Available at: . [Last accessed April 2024]. 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: April 2024]. Clinicaltrials.gov. Efficacy and Safety Study of Benralizumab in Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID). Available at: . [Last accessed: April 2024]. 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: April 2024]. Airsupra (albuterol/budesonide) US prescribing information; 2022. Corren J, et al. Tezepelumab in adults with uncontrolled asthma [supplementary appendix; updated April 18, 2019]. 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: . [Last accessed: April 2024]. AstraZeneca plc. Tezspire approved in the EU for the treatment of severe asthma. 2022. Available at: . [Last accessed: April 2024]. AstraZeneca plc. Tezspire approved in Japan for the treatment of severe asthma. Available at: . [Last accessed: April 2024]. View source version on businesswire.com: Contacts Media Inquiries Brendan McEvoy +1 302 885 2677 Jillian Gonzales +1 302 885 2677 US Media Mailbox: usmediateam@astrazeneca.com Source: AstraZeneca View this news release online at:

▲3月7-8日 成都生物医药创新者峰会 · 点击立即报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。临床试验的失败可能源于多个方面，一项研究表明90%的药物开发临床失败可能有四个原因：缺乏临床疗效（40%-50%）、难以控制的毒性（30%）、类药特性差（10%-15%)，以及缺乏商业需求和战略规划不佳(10%)，包括临床疗效不佳、安全性问题等[1]。据不完全统计，2024年1-2月约有18个失败临床研究，其中12项研究因未达主要研究终点告终。01亚虹医药：APL-1202治疗化疗灌注复发的中高危非肌层浸润性膀胱癌的关键性临床试验2月5日，亚虹医药发布公告宣布其产品APL1202与化疗灌注联合使用治疗化疗灌注复发的中高危非肌层浸润性膀胱癌（NMIBC）的随机、双盲、对照、多中心的关键性临床试验未达到主要研究终点，公司决定终止APL-1202与化疗灌注联合使用在该适应症的进一步开发。APL-1202（商品名唯施可®）是一款口服的可逆性MetAP2抑制剂，具有抗血管生成、抗肿瘤活性及调节肿瘤免疫微环境的作用。此研究是一项随机、双盲、对照、多中心的关键性临床试验，主要研究终点是无事件生存期（EFS，“事件”定义为经病理确认的复发、进展或膀胱癌引起的死亡）。结果显示，尽管在部分患者人群中显示出一定的优效趋势，但是主要疗效指标无事件生存期（EFS）未达到预设的统计假设。除本研究外，公司同时正在开展APL-1202其他2项临床试验。APL-1202单药治疗未经治疗的中危NMIBC的Ⅲ期临床试验（Ascertain）处于临床入组阶段。APL-1202口服联合替雷利珠单抗作为肌层浸润性膀胱癌（MIBC）新辅助治疗的II期临床试验（Anticipate）已经完成所有受试者入组，预计2024年三季度读出Ⅱ期顶线数据。Anticipate研究已完成Ⅱ期临床试验期中分析，结果达到了方案预设要求。02Gilead：magrolimab治疗急性髓性白血病的Ⅲ期ENHANCE-3研究2月7日，Gilead宣布终止CD47单抗magrolimab治疗急性髓性白血病（AML）的3期ENHANCE-3研究，FDA将所有magrolimab治疗骨髓增生异常综合征（MDS）和急性髓性白血病的研究，包括相关的扩大准入项目置于全面临床搁置状态。这些决定是根据独立数据监测委员会的建议做出的，该委员会审查了ENHANCE-3总生存期（OS）中期分析计划的一线数据。在该分析中，magrolimab与阿扎胞苷和venetoclax联用显示出无治疗效果，并观察到死亡风险增加，主要是由感染和呼吸衰竭引起的。另外两项针对高风险MDS（ENHANCE）和TP53突变AML（ENHANCE-2）的临床研究数据的初步分析也表明，在magrolimab治疗组中，患者死亡风险增加，并且药物无治疗效果，基于这些结果吉利德表示将不再进一步开发magrolimab用于治疗血液病。03Synlogic：SYNB1934治疗苯丙酮尿症的Ⅲ期 Synpheny-3研究2月8日，Synlogic公司（纳斯达克股票代码：SYBX）宣布终止Synpheny-3研究，该研究是对labafenogene marselecobac (SYNB1934)作为苯丙酮尿症（PKU）的一种潜在治疗方法正在进行的Ⅲ期临床研究。SYNB1934是利用合成生物学改造的细菌菌株，具有降解苯丙氨酸的能力。终止Synpheny-3试验的决定是基于即将进行的独立数据监测委员会（DMC）评估前的内部审查结果，该结果表明该试验不太可能达到主要终点。该决定并非基于对安全性或耐受性的担忧。Synlogic现在将与相关的Synpheny-3临床试验机构合作，执行终止试验的决定。04阿斯利康：Tozorakimab联合达格列净治疗糖尿病肾病的IIb期临床研究2月8日，阿斯利康在2023年全年业绩报告上公布因疗效不佳，决定终止抗IL-33单抗Tozorakimab联合达格列净治疗糖尿病肾病的IIb期临床研究（NCT04170543）。这项研究旨在评估MEDI3506在标准治疗基础上对糖尿病肾病患者的疗效和安全性。首要目标是评估MEDI3506对糖尿病肾病成年受试者白蛋白尿的影响，次要目标包括评估安全性、PK、治疗期间ADA的发生率。05AN2 Therapeutics：epetraborole治疗难治性肺病的II/III期EBO-301研究2月12日，AN2 Therapeutics宣布自愿暂停无缝II/III期临床试验（EBO-301）中III期研究部分的患者入组，该试验旨在评估口服小分子细菌leucyl-tRNA合成酶抑制剂epetraborole治疗由鸟分枝杆菌复合体（MAC）引起的难治性肺病的疗效与安全性。这项双盲、安慰剂对照的临床试验共分为两个队列，对比epetraborole+优化背景方案（OBR）与安慰剂+OBR的疗效。II期研究部分已于2023年9月完成了80例患者的入组，III期研究部分迄今为止招募了近100例患者，已入组患者将被允许继续参与研究。在对正在进行的第二阶段研究进行盲法汇总分析后，发现疗效可能低于预期，因此决定自愿暂停试验。这一决定并非出于安全考虑，2期试验的目的是为3期试验提供依据。公司预计将于2024年夏季公布2期试验的初步数据。06大冢制药：AVP-786治疗阿尔茨海默病痴呆相关激越的III期临床研究2月12日，大冢制药公布了AVP-786（氘代右美沙芬+奎尼丁）治疗阿尔茨海默病痴呆相关激越的III期临床试验（NCT03393520）未达主要疗效终点。AVP-786是氘代的氢溴酸右美沙芬和CYP2D6抑制剂硫酸奎尼丁的复方制剂。据观察，氘化可显著降低对细胞色素P450（CYP2D6）酶代谢的敏感性，从而提高生物利用度。在主要疗效终点（Cohen-Mansfield激越量表（CMAI）总分从基线到第12周的平均变化）上，AVP-786和安慰剂之间没有达到统计学意义上的显著差异。07Roivant Sciences：RVT-2001用于治疗骨髓增生异常综合征的I/II期试验2月13日，Roivant Sciences在财报中披露终止开发SF3B1调节剂RVT-2001用于治疗骨髓增生异常综合征的临床I/II期试验，原因是期中分析结果后有效性不及预期。2022年，Roivant与卫材（Eisai）达成了一项许可协议，获得在研药物RVT-2001的全球独家权利，RVT-2001是一款潜在的first-in-class口服小分子剪接因子SF3B1调节剂，RVT-2001已经在19例低风险、输血依赖性MDS患者中，让超过30%的患者不依赖血红细胞输注。08Denali/赛诺菲：DNL788治疗肌萎缩侧索硬化症的II期HIMALAYA研究2月16日，Denali Therapeutics在SEC文件中透露，DNL788（SAR443820）治疗肌萎缩侧索硬化症（ALS）的II期HIMALAYA研究未能达到显著改善修订版ALS功能评定量表（ALSFRS-R）评分的主要终点。受此消息影响，Denali的股价下跌了近8%。2018年10月，赛诺菲和Denali公司就RIPK1抑制剂的全球开发和商业化展开广泛合作。赛诺菲将领导SAR443820/DNL788治疗ALS和MS的1期临床和2期临床开发，并与Denali公司一起进行该药治疗ALS、MS和阿尔茨海默病的3期临床试验。SAR443820/DNL788是由赛诺菲和Denali共同开发的一款有效的、选择性的、具有脑渗透性的RIPK1抑制剂。赛诺菲将继续在多发性硬化症患者中开展SAR443820/DNL788的K2 2期研究；1月8日，Denali在新闻稿中透露，赛诺菲已完成SAR443820/DNL788治疗多发性硬化症（MS）的2期试验，共招募174名参与者。09Theravance Biopharma：Yupelri治疗COPD的IV期PIFR-2研究2024年1月5日，Theravance Biopharma宣布Yupelri（revfenacin）吸入溶液用于慢性阻塞性肺病（COPD）维持治疗的IV期PIFR-2研究未达主要终点。Yupelri 是美国批准用于慢阻肺维持治疗的唯一每日一次的雾化长效毒蕈碱拮抗剂（LAMA）。这项PIFR-2研究旨在评估，Yupelri较噻托溴铵（Spiriva，粉雾剂）在严重至极为严重COPD患者的肺功能改善情况。研究结果显示，第85天时第一秒用力呼气谷值较基线变化的主要终点指标方面，与对照组相比，Yupelri并未有统计学显著差异。Yupelri的安全性与耐受性与既往研究一致。本次研究的失败也导致Theravance股价下跌10%。10Allakos：lirentelimab治疗特应性皮炎的II期ATLAS研究和治疗慢性自发性荨麻疹的IIb期MAVERICK研究1月16日，Allakos宣布lirentelimab在治疗特应性皮炎患者的2期临床试验（ATLAS）和治疗慢性自发性荨麻疹患者的2b期临床试验（MAVERICK）中均未达主要终点。Lirentelimab治疗特应性皮炎患者的2b期临床试验（ATLAS）研究结果显示，在主要终点治疗后达到EASI-75上，接受Lirentelimab治疗的患者达到EASI-75的患者比例为23%，而接受安慰剂治疗的患者中这一比例为18%，不具有统计学意义。在MAVERICK试验中，主要终点UAS7减少比例上，Lirentelimab治疗患者的UAS7减少了27%，而安慰剂治疗患者中这一比例为26%，也不具有统计学意义。11Gilead：Trodelvy治疗经治转移性或晚期非小细胞肺癌的III期EVOKE-01研究2024年1月22日，Gilead公布Trop2 ADC新药Trodelvy治疗非小细胞肺癌的三期临床EVOKE-01研究没有达到OS主要终点。EVOKE-01正在评估Trop2 ADC药物Trodelvy®（sacituzumab-govitecan-hziy；SG）与多西他赛在铂类化疗和检查点抑制剂治疗期间或之后进展的转移性或晚期NSCLC患者中的疗效。Trodelvy是一款Trop-2 ADC单抗药物。Trop-2是一种跨膜糖蛋白，它的高表达与很多肿瘤的发生以及预后较差相关，是一个非常热门的ADC研究靶点，热度仅次于HER2。目前全球只有吉利德的Trop-2 ADC药物Trodelvy获批上市，用于治疗既往接受过至少2种疗法的转移性三阴乳腺癌（mTNBC）成人患者和局部晚期或转移性尿路上皮癌（UC）患者。Trodelvy的试败导致吉利德股价在达到11个月高点后，周一暴跌约10%。12BMS：Opdivo治疗肌萎缩侧索硬化症的III期CheckMate-914研究1月29日，百时美施贵宝（BMS）宣布其PD-1抑制剂Opdivo在III期CheckMate-914研究的B部分中失败，对于术后存在高复发风险的局部肾细胞癌患者未带来显著的无病生存益处。CheckMate-914是一项随机、双盲、两部分的试验。在B部分中，该研究将Opdivo单药疗法与安慰剂对比。此试验评估其作为肾细胞癌（RCC）患者的辅助治疗。这些患者已经完全或部分切除肾脏，并且处于中度或高度复发风险。在中位随访27个月后，Opdivo未能在病情无进展生存期（DFS）方面取得显著改善，根据盲目独立中央审查（BICR）的评估，与安慰剂相比，Opdivo的效果呈现出0.87的风险比，p值为0.3952。在Opdivo组的12个月DFS概率为83.3%，而安慰剂组为78.2%。在18个月时，这些估计仅略有变化，分别为78.4%和75.4%。在分析时，两个治疗组的DFS中位数均未达到。13来凯医药：afuresertib联合紫杉醇治疗耐药卵巢癌的II期临床研究1月29号，来凯医药公布afuresertib联合紫杉醇治疗耐药卵巢癌（PROC）（PROFECTA-II）的顶线数据。PROFECTA-II研究（NCT04374630）是一项随机、开发标签、有效对照的2期临床试验，评估afuresertib合紫杉醇治疗与单独紫杉醇对照铂耐药卵巢癌（PROC）女性患者的疗效和安全性。研究在美国和中国随机入组了150名患者到试验组和对照组。主要终点为研究者评估的无进展生存期，次要终包括总生存期、客观缓解率和持续缓解时间。试验结果表明，afuresertib联合紫杉醇治疗可以降低疾病展或死亡的风险（无进展生存期，PFS )，HR为0.744（95%CI:0.502-1.102），但试验结果不具有统计学意义。总结据公开资料显示，2024年伊始已有18款药物在临床中折戟，终止临床二期和临床三期试验的原因中疗效仍然是最关键的原因，在肿瘤和CNS疾病中这一比例更大，这也反映出这些疾病的复杂性和异质性，仍需更多耐力去克服。虽然II期试验中因安全性原因导致失败的比例有所增加，但在III期中，这一原因的占比正在减少，这说明研发越来越在安全性下功夫，可以在研发早期就筛除安全性差的产品。在研发新药的路上只有战胜挫折，拥有接受困难的勇气，才有机会让罹受疾病困扰的人民重获新生。参考文献：[1]Sun D, Gao W, Hu H, Zhou S. Why 90% of clinical drug development fails and how to improve it?. Acta Pharm Sin B. 2022;12(7):3049-3062.[2]各公司官网版权声明：本文转自生物药大时代，如不希望被转载的媒体或个人可与我们联系，我们将立即删除 活动推荐  3月 • NDC x 2024新药创新者峰会  关键词：  ADC，改良型新药，小分子新药，GLP-1药物（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。