Budesonide/Formoterol fumarate/Glycopyrronium Bromide

AstraZeneca's inhaler Breztri Aerosphere, which was approved for COPD in 2020, has taken a step toward a label expansion as it has aced two asthma trials. AstraZeneca has taken a key step in advancing Breztri Aerosphere toward a potential label expansion and achieving its goal of annual sales of $3 billion to $5 billion for the 3-in-1 inhaler.Two phase 3 trials evaluating the effectiveness and safety of Breztri in a total of 4,434 patients with uncontrolled asthma have met their primary endpoints. The studies showed that Breztri delivered statistically significant and clinically meaningful improvements in lung function compared to dual-drug combinations of inhaled corticosteroid (ICS) and long-acting beta2-agonist (LABA) maintenance treatments, AZ said.Data from the KALOS and LOGOS studies will be shared with regulatory authorities and presented at an upcoming medical meeting, the company added.Breztri Aerosphere, which was approved for chronic obstructive pulmonary disorder (COPD) in 2020, is a fixed-dose combination of the corticosteroid budesonide, the LABA formoterol fumarate and the long-acting muscarinic antagonist (LAMA) glycopyrronium.With sales (PDF) of $300 million in the first quarter of 2025, an increase of 37% year over year, Breztri is on its way to blockbuster status for the first time this year.A label expansion to treat asthma would open the treatment up to another large patient population. The condition affects roughly 262 million people around the world, AZ said, with nearly half of those treated with dual therapies remaining uncontrolled. “Despite advancements in asthma treatments, millions of patients remain uncontrolled, which can cause frequent breathlessness, coughing and wheezing,” Alberto Papi, of the St. Anna University Hospital in Ferrara, Italy, said in a press release. “The results from the KALOS and LOGOS trials are exciting and demonstrate the potential of Breztri to evolve the standard of care to more effectively treat asthma in a single inhaled triple therapy.”Breztri was developed as a combination of AZ’s blockbuster Symbicort (budesonide/formoterol), which was approved for asthma in 2006, and Bevespi (formoterol fumarate/glycopyrrolate), which was approved for COPD in 2016. In its development, Breztri has trailed GSK’s triple therapy Trelegy Ellipta, which was approved for COPD in 2017 and for asthma in 2020. Trelegy generated sales of $3.5 billion in 2024, an increase of 26%. GlobalData forecasts that sales of Breztri will reach $2.3 billion in 2030.Breztri is one of several treatments AZ is developing for respiratory diseases, including Fasenra and Amgen-partnered Tezspire. Both of those drugs have been approved to treat asthma and AZ is eying potential COPD label expansions. Fasenra achieved sales of $1.7 billion last year. AZ reported sales for fast-rising Tezspire, which was approved in 2021, at $684 million.

WILMINGTON, Del.--(BUSINESS WIRE)--Positive high-level results from the Phase III KALOS and LOGOS trials in patients with uncontrolled asthma showed that AstraZeneca’s fixed-dose triple-combination therapy BREZTRI AEROSPHERE (budesonide/glycopyrronium/formoterol fumarate or BGF (320/28.8/9.6μg)) met all primary endpoints, demonstrating a statistically significant and clinically meaningful improvement in lung function compared with dual-combination inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) medicines. KALOS and LOGOS were replicate, randomized, double-blind trials designed to investigate BREZTRI as a potential treatment for asthma.1,2 The trials evaluated the efficacy and safety of BREZTRI versus maintenance treatment with ICS/LABA in adults and adolescents with uncontrolled asthma.1,2 Asthma is a common, chronic respiratory disease characterized by inflammation and muscle tightening in the airway (bronchoconstriction), which can make it difficult to breathe.3 As many as 262 million people worldwide are affected by asthma,3 and it is estimated that nearly half of those treated with dual therapy remain uncontrolled, which can significantly limit lung function and decrease quality of life.4,5 Alberto Papi, Professor and Chair of Respiratory Medicine at the University of Ferrara, and Director of the Respiratory Unit, CardioRespiratory Department, S. Anna University Hospital, Ferrara, Italy, and primary investigator, said: “Despite advancements in asthma treatments, millions of patients remain uncontrolled, which can cause frequent breathlessness, coughing and wheezing, significantly impacting their ability to perform daily activities. The results from the KALOS and LOGOS trials are exciting and demonstrate the potential of budesonide/glycopyrronium/formoterol to evolve the standard of care to more effectively treat asthma in a single inhaled triple therapy for patients who remain uncontrolled with dual maintenance therapy.” Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “We are excited by the positive results from the KALOS and LOGOS trials, which demonstrate that BREZTRI could help improve the lives of the millions of patients living with asthma. These asthma data build on the well-established profile of BREZTRI in COPD, and we look forward to sharing with regulatory authorities to bring this important medicine to a wider group of patients.” There were no new safety or tolerability signals identified for BREZTRI in KALOS or LOGOS. Full results from the two Phase III trials will be shared with regulatory authorities and presented at an upcoming medical meeting. BREZTRI is an inhaled triple-combination therapy approved for the treatment of chronic obstructive pulmonary disease (COPD) in adults in more than 80 countries worldwide including the US, EU, China and Japan. IMPORTANT SAFETY INFORMATION 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 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. Notes Asthma Asthma is a prevalent, chronic respiratory disease affecting as many as 262 million people worldwide,3 including over 25 million in the US.6 When uncontrolled, inflammation and muscle tightening in the airway (bronchoconstriction) may cause wheezing, breathlessness, chest tightness, coughing, and even death.3,7 Many patients remain uncontrolled despite the availability of standard of care medicines and continue to experience significant limitations on lung function and reduced quality of life.4,5 KALOS and LOGOS Phase III trials KALOS and LOGOS are replicate confirmatory, randomized, double-blind, double-dummy, parallel group, multi-centre, 24-to-52-week variable length Phase III trials to assess the efficacy and safety of BGF (320/28.8/9.6μg and 320/14.4/9.6μg) compared with two fixed-dose, dual-combination therapies of budesonide, an ICS, and formoterol fumarate, a LABA: PT009 (in an AEROSPHERE inhaler) and SYMBICORT pressurized metered-dose inhaler (pMDI).1,2 KALOS and LOGOS included approximately 4,400 randomized patients. The trial design was optimized to evaluate the 320/28.8/9.6μg dose of BGF. The primary efficacy endpoints for the two individual trials were a change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24 and trough FEV1 over 12-24 weeks and over 24 weeks.1,2 In addition to the two registrational trials, KALOS and LOGOS, two qualifying trials, LITHOS and VATHOS,8,9 also met their primary endpoints. LITHOS and VATHOS included approximately 1,000 randomized patients. AstraZeneca in Respiratory & Immunology Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals is a key disease area and growth driver to the Company. AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca. References Clinicaltrials.gov. Study to Assess PT010 in Adult and Adolescent Participants with Inadequately Controlled Asthma (KALOS) [Online]. Available at: https://clinicaltrials.gov/study/NCT04609878?limit=25&term=KALOS&rank=1 . [Last accessed: May 2025]. Clinicaltrials.gov. Study to Assess PT010 in Adult and Adolescent Participants with Inadequately Controlled Asthma (LOGOS) [Online]. Available at: https://clinicaltrials.gov/study/NCT04609904?limit=25&term=LOGOS&rank=4 . [Last accessed: May 2025]. Global Asthma Network. The Global Asthma Report 2022. [Online]. Available at: http://globalasthmareport.org/resources/Global_Asthma_Report_2022.pdf . [Last accessed: May 2025]. Davis J, et al . Burden of asthma among patients adherent to ICS/LABA: A real-world study. J Asthma . 2019 Mar;56(3):332-340. Buhl R, et al . One-year follow up of asthmatic patients newly initiated on treatment with medium- or high-dose inhaled corticosteroid-long-acting β2-agonist in UK primary care settings. Respir Med . 2020 Feb: 162:105859. U.S. Centers for Disease Control and Prevention (CDC). Most Recent National Asthma Data. [Online]. Available at: https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm . [Last accessed: May 2025]. Fernandes AG, et al . Risk factors for death in patients with severe asthma. J Bras Pneumol . 2014; 40 (4): 364-372. Clinicaltrials.gov. A 12-week Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Metered Dose Inhaler Relative to Budesonide Metered Dose Inhaler in Participants with Inadequately Controlled Asthma (LITHOS) [Online]. Available at: https://clinicaltrials.gov/study/NCT05755906?limit=25&term=LITHOS&rank=1 . [Last Accessed: May 2025]. Clinicaltrials.gov. A 24-Week Efficacy and Safety Study to Assess Budesonide and Formoterol Fumarate Metered Dose Inhaler in Adult and Adolescent Participants with Inadequately Controlled Asthma (VATHOS) [Online]. Available at: https://clinicaltrials.gov/study/NCT05202262?limit=25&term=VATHOS&rank=1 . [Last Accessed: May 2025]. AstraZeneca Data on File. 2025. REF-270910. Last Updated 4/2025