AstraZeneca data at ERS 2023 demonstrate leadership in transforming care across a broad respiratory portfolio of inhaled and biologic medicines

New data from FASENRA and TEZSPIRE trials demonstrate AstraZeneca biologics progress towards achieving remission in severe asthma

New EXACOS-CV data uncover increased cardiopulmonary risk following COPD exacerbations

AstraZeneca will present new clinical and real-world data across its leading inhaled, biologic and early science respiratory portfolio at the European Respiratory Society (ERS) International Congress 2023, in Milan, Italy from September 9 to 13, 2023. The company will present 93 abstracts, including 18 oral presentations, which will focus on unmet needs in severe asthma, chronic obstructive pulmonary disease (COPD) and other acute respiratory diseases.  

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, AstraZeneca, said: “Unlike many other immune-mediated diseases, remission is not a well-established treatment goal in asthma. Key data presented at ERS investigate FASENRA and TEZSPIRE’s potential to achieve remission in asthma, elevating care and further improving patient lives. Across our data we will showcase the significant steps we’ve made towards transforming care in asthma, COPD and other respiratory diseases.”

The definition of clinical remission as a treatment goal in severe asthma generally includes the following criteria: no exacerbations, no maintenance oral corticosteroid use, stable lung function and sustained absence of significant asthma symptoms.¹

Advancing the science for FASENRA (benralizumab), a leading biologic for the treatment of severe eosinophilic asthma (SEA)²

• SHAMAL Phase IV trial: the late-breaking presentation is the first-ever trial to investigate the potential of a targeted biologic treatment to enable a significant step down of inhaled corticosteroid (ICS) therapy in severe asthma patients.³
• BORA Phase III extension trial and real-world XALOC program: separate analyses will support clinical remission as an achievable and sustainable goal for patients with SEA over two years of treatment with FASENRA.^4,5
• MIRACLE Phase III trial: late-breaking data will evaluate the efficacy and safety of FASENRA among patients with uncontrolled SEA in China and other Asian countries, where the condition is largely underdiagnosed and undertreated.^6,7 High-level results from the trial demonstrated a clinically and statistically significant reduction in asthma exacerbation rate.⁸

Demonstrating TEZSPIRE’s (tezepelumab) potential to deliver sustained remission in a broad severe asthma patient population

• DESTINATION Phase III post-hoc exploratory analysis: the analysis shows TEZSPIRE’s ability to deliver sustained remission vs. placebo over a two-year period in a broad patient population with no phenotype or biomarker limitations.⁹
• Off treatment DESTINATION Phase III extension: this analysis demonstrates that the sustained effects of TEZSPIRE gradually decrease after stopping treatment with neither the biomarkers nor the clinical effects returning to baseline after nine months since last dose. The results show the importance of long-term use of TEZSPIRE.¹⁰

Highlighting the urgency to prevent COPD exacerbations with new real-world data on cardiopulmonary risk  

• EXACOS-CV multi-country retrospective cohort study: new real-world data from over 300,000 patients with COPD demonstrate that patients who experienced an exacerbation had an increased risk of serious cardiovascular events in the first six months, and this risk remained elevated for one year.¹¹ These data highlight the importance of preventing COPD exacerbations to reduce cardiopulmonary risk and mortality.¹²

Early pipeline scientific advancements

• Cytokine, interleukin-33 (IL-33) research: new efficacy and safety results from the ACCORD-2 Phase IIa trial will add to the growing evidence for tozorakimab, an IL-33 neutralising monoclonal antibody, as a potential treatment option for patients hospitalized with COVID-19.^13,14    
  • Exploratory research will be shared demonstrating the potential of a new platform to investigate IL-33 biology and screen novel therapies.¹⁵
• Early COPD research: new approaches to identify biological drivers of early COPD disease to improve earlier diagnosis.¹⁶

Key AstraZeneca presentations during ERS 2023:

BREZTRI AEROSPHERE^® (budesonide/glycopyrronium/formoterol fumarate) Important Safety Information

• 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.

TEZSPIRE^® (tezepelumab-ekko) Important Safety Information

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 by clicking here.

FASENRA^® (benralizumab) 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 www.mothertobaby.org/fasenra.

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 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.

Severe asthma

Severe asthma is an often-debilitating, potentially fatal condition affecting up to 26 million people worldwide.^17-20 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.^17,19-21  

COPD

COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems.¹² It affects an estimated 391 million people around the world and is the third leading cause of death globally.^22,23

FASENRA
FASENRA (benralizumab) 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 eosinophils via apoptosis (programmed cell death).²⁴ FASENRA is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries, and is approved for self-administration in the US, EU and other countries. Results from the MIRACLE Phase III trial will support our application for the review of FASENRA as a treatment for severe asthma to the China National Medical Products Administration (NMPA).

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.^25,26 TEZSPIRE is approved in the US, EU, Japan and other countries for the treatment of severe asthma.^27-29

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.

BREZTRI/AEROSPHERE

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 pressurized 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.

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 (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 astrazeneca.com and follow the Company on social media @AstraZeneca.

Contacts

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References

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