New AstraZeneca Data Presented at ATS 2023 Strengthen the Body of Evidence Supporting Early Intervention With BREZTRI in COPD

EROS real-world outcomes data show prompt initiation of BREZTRI is associated with a reduced risk of future exacerbations in people living with COPD¹

EXACOS-CV US data highlights increased risk of severe cardiovascular events following an acute COPD exacerbation²

WILMINGTON, Del.--(BUSINESS WIRE)--Results from the EROS real-world retrospective study showed that initiating fixed-dose triple-combination therapy BREZTRI AEROSPHERE^® (budesonide/glycopyrronium/formoterol fumarate) within 30 days of a qualifying moderate or severe exacerbation in patients with COPD (chronic obstructive pulmonary disease) is associated with a decreased risk of future exacerbations by 24% vs. delaying treatment by one to six months, and by 34% vs. delaying treatment six months to one year.¹

The EROS study is the first real-world evidence analysis of BREZTRI in more than 2,400 patients with COPD from a claims database registry, and was presented today as a late-breaking abstract at the ATS 2023 International Conference in Washington, DC, hosted by the American Thoracic Society. AstraZeneca's presence at ATS 2023 also includes new data from TEZSPIRE and FASENRA.

Professor Charlie Strange, MD, Medical University of South Carolina, US and investigator in the EROS study, said: "A key treatment goal in COPD is to avoid exacerbations that may lead to increased risk of future exacerbations, possible hospitalization or even death. The EROS real-world data build on the body of clinical evidence that BREZTRI is effective in reducing COPD exacerbation rates and can significantly reduce the risk of future exacerbations if used as soon as a patient’s COPD symptoms worsen.”

Another late-breaking presentation at ATS 2023, the EXACOS-CV US retrospective cohort study using the HealthCore Integrated Research Database of people with COPD showed the risk of an acute severe cardiovascular (CV) event (including stroke, heart failure, pulmonary embolism, arrhythmia, or heart attack) increased by 32% in the first 30 days following a single acute moderate or severe COPD exacerbation, compared to those without a prior COPD exacerbation. According to the results, the risk of CV events was highest in the first 90 days following the COPD exacerbation, the risk remained elevated for one year, and each subsequent COPD exacerbation was associated with an even higher risk of acute CV events (>2 times increased CV risk following two or three COPD exacerbations).² These results suggest that patients with COPD should be considered at risk of cardiopulmonary events following an acute exacerbation, even those who are newly-diagnosed.

Robert Fogel, Vice President, Global Medical Affairs, Respiratory & Immunology, AstraZeneca, said: “As the third leading cause of death worldwide³, improving outcomes for patients must be an urgent priority for physicians and healthcare systems. The EROS and EXACOS-CV studies increase our understanding of the significant cardiopulmonary risk COPD patients face as well as the opportunity to reduce COPD exacerbations through more proactive treatment with BREZTRI.”

AstraZeneca Respiratory & Immunology pipeline and portfolio highlighted in more than 50 abstracts at ATS 2023

Key additional data from AstraZeneca at ATS include:

• Two post hoc analyses from the NAVIGATOR Phase III trial demonstrating efficacy of TEZSPIRE in patients with severe, uncontrolled asthma irrespective of prior omalizumab use; and in improving rhinosinusitis symptoms measured with SNOT-22 in patients who also have a history of comorbid nasal polyps.^4,5
• Real-world evidence from the retrospective RANS trial supporting the strong clinical efficacy of FASENRA specifically in patients with severe eosinophilic asthma and nasal polyps; and a post-hoc analysis of five FASENRA Phase III/IIIb trials showing an increased rate of achieving clinical remission in patients with severe eosinophilic asthma and concomitant nasal polyps.^6,7

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

COPD
COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems.⁸ It affects an estimated 391 million people around the world and is the third leading cause of death globally.^3,9

EROS
The EROS (Exacerbations and Real-World Outcomes) study is a retrospective analysis of real-world outcomes in 2,409 COPD patients appearing in the MORE² Registry^® claims database in the US to examine whether prompt initiation of BREZTRI following an exacerbation lowers risk of future exacerbations compared to delayed and very delayed initiation.¹ In the study, qualifying exacerbations included: one moderate exacerbation while on maintenance treatment, the second of two moderate events without any maintenance treatment, and severe events defined as COPD hospitalizations.

EXACOS-CV US
EXACOS-CV US (EXACerbations and their OutcomeS – CardioVascular) is a retrospective cohort study of 355,978 patients 40 years and older who were diagnosed with COPD between 1 January 2012 and 31 December 2019. The study used US administrative claims data from the Healthcare Integrated Research Database, managed by Carelon Research (formerly HealthCore), to investigate a correlation between cardiovascular events and moderate-to-severe COPD exacerbations.²

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 in a 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.

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.^10,11 TEZSPIRE is approved in the US, EU, Japan and other countries for the treatment of severe asthma.^12-14

NAVIGATOR
NAVIGATOR is a Phase III, randomized, double-blinded, placebo-controlled trial to evaluate the efficacy and safety of TEZSPIRE (210mg every four weeks) compared to placebo added to SoC in adults and adolescents with severe, uncontrolled asthma.¹⁵ Two post hoc analyses from the NAVIGATOR trial evaluated the effect of TEZSPIRE on the annualized asthma exacerbation rate (AAER) over 52 weeks with and without prior omalizumab, and changes in total and domain SNOT-22 scores from baseline to week 52 in patients with a history of nasal polyps.^4,5

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.

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).¹⁶ 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.

FASENRA was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan.

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 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on Twitter @AstraZenecaUS.

References

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2. Daniels, K, Tave, A., Neikirk, A., et al. Incidence of acute cardiovascular events following acute exacerbation of chronic obstructive pulmonary disease in a large US claims database [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2023 (19-24 May).
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4. Menzies-Gow, A, Colice, G, Ambrose, C, et al. Efficacy of tezepelumab in patients with severe, uncontrolled asthma by prior omalizumab use: a post hoc analysis of the phase 3 NAVIGATOR study. [Mini Symposium] Presented at the American Thoracic Society International Conference 2023 (19-24 May)
5. Spahn, J, Jacobs, J, Hoyte, F, et al. Tezepelumab efficacy by SNOT-22 domain scores in patients with severe, uncontrolled asthma and comorbid nasal polyps in the phase 3 NAVIGATOR study. [Poster Discussion] Presented at the American Thoracic Society International Conference 2023 (19-24 May)
6. Le TT, et al. Real-World Evidence of Benralizumab in Patients with Severe Eosinophilic Asthma and Nasal Polyps: Initial Results of the RANS Study. [Poster discussion]. Presented at the American Thoracic Society International Conference 2023, 23 May 2023, 14:15-16:15 EST
7. Louis R, et al. Approaching clinical remission in severe asthma: An analysis of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with benralizumab across five clinical trials. [Poster discussion]. Presented at the American Thoracic Society International Conference 2023, 23 May 2023, 9:00-16:15 EST
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10. Corren J, et al. Tezepelumab in adults with uncontrolled asthma [supplementary appendix; updated April 18, 2019]. N Engl J Med. 2017;377:936-946.
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12. AstraZeneca plc. Tezspire (tezepelumab) approved in the US for severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/Tezspire-tezepelumab-approved-in-the-us-for-severe-asthma.html. [Last accessed: May 2023].
13. AstraZeneca plc. Tezspire approved in the EU for the treatment of severe asthma. 2022. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/tezspire-approved-in-the-eu-for-the-treatment-of-severe-asthma.html. [Last accessed: May 2023].
14. AstraZeneca plc. Tezspire approved in Japan for the treatment of severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-japan-for-severe-asthma.html. [Last accessed: May 2023].
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16. AstraZeneca. Fasenra Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/fasenra-epar-product-information_en.pdf [Last accessed: May 2023].