FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of April 2026
Commission
File Number: 001-11960
AstraZeneca PLC
1
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Third tozorakimab positive Phase III in COPD
20 April 2026
Tozorakimab met primary endpoint in Phase III MIRANDA trial in
patients with COPD
Third positive pivotal Phase III clinical trial of AstraZeneca's
IL-33-targeting biologic further demonstrates its benefits in
COPD
Positive high-level results from the pivotal Phase III MIRANDA
trial showed potential first-in-class tozorakimab demonstrated a
statistically significant and clinically meaningful reduction in
the annualised rate of moderate-to-severe COPD exacerbations in the
primary population of former smokers and in the overall population,
which included former and current smokers, and patients across
all blood eosinophil* counts and all stages of lung function
severity.
In MIRANDA, patients received tozorakimab 300mg or placebo on top
of standard of care once every two weeks.1 The
trial enrolled patients with COPD still experiencing
moderate-to-severe exacerbations while on inhaled standard of
care.1 These
results follow an announcement in
March of the positive high-level results from the pivotal Phase III
OBERON and TITANIA trials studying tozorakimab at a four-week
dosing interval.
Frank Sciurba, MD, FCCP, Professor of Pulmonary and Critical Care
Medicine, University of Pittsburgh, Chief Investigator of LUNA
programme said: "These results add to the growing body of
evidence that indicates tozorakimab delivered meaningful clinical
benefits for COPD patients who urgently need new treatment options.
Up to half of patients today still experience exacerbations even
when taking standard-of-care inhaled therapies, putting them at
risk of serious health consequences including hospitalisation and
even death."
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D,
AstraZeneca, said: "These data further demonstrate tozorakimab's
exciting potential as a first-in-class biologic with a truly
differentiated mechanism of action that inhibits the signalling of
the reduced and oxidised forms of IL-33 to address underlying
drivers of COPD. We look forward to sharing the data with
regulators and the scientific community as soon as
possible."
Tozorakimab was generally well tolerated with a favourable safety
profile consistent with previous trials. The data will be
submitted to regulatory authorities and shared with the scientific
community at an upcoming medical meeting.
Nearly 400 million people are diagnosed with COPD, a heterogenous
and progressive disease and the 3rd leading
cause of death globally.2,3 Even
when on inhaled standard of care, more than 50% of patients
experience exacerbations, putting them at an increased risk of
cardiopulmonary events and mortality.4-7
Tozorakimab is a potential first-in-class monoclonal antibody
targeting interleukin-33 (IL-33), that uniquely inhibits the
signalling of the reduced and oxidised forms of IL-33, offering the
potential to both reduce inflammation and disrupt the cycle of
mucus dysfunction that contribute to COPD
worsening.8-11
Tozorakimab is also being studied in a Phase III trial for severe
viral lower respiratory tract disease and in a Phase II trial in
asthma.12,13
*eosinophil: a type of white blood cell, which at increased
levels may contribute to inflammation in respiratory
diseases.14
Notes
COPD
COPD, the third leading cause of death (excluding COVID-19)
worldwide, is a progressive respiratory condition characterised by
persistent airflow limitation and chronic inflammation of the
airways.3,15 Common
symptoms include breathlessness, chronic cough and excess mucus
production.15 These
symptoms can worsen over time and contribute to ongoing
inflammation and bronchoconstriction, making it difficult to
breathe and increasing the risk of COPD
exacerbations.15 These
COPD exacerbations have a profound impact on the lives of those
with the disease, accelerating disease progression, increasing
hospitalisations, and increasing the risk of future cardiopulmonary
events - including heart attacks, all of which can be
life-threatening.7,15 In
the US, exacerbations cause more than 2,500 emergency department
visits per day.16 Only
50% of COPD patients live more than 3.5 years after their first
severe exacerbation.17
Phase III LUNA programme
Tozorakimab's Phase III COPD development programme includes four
clinical trials: OBERON, TITANIA, MIRANDA and
PROSPERO.
OBERON and TITANIA
OBERON and TITANIA are replicate Phase III double-blind,
placebo-controlled trials investigating the efficacy and safety of
tozorakimab in adults with symptomatic COPD with a history of
≥2 moderate or ≥1 severe COPD exacerbations in the 12
months prior to enrolment. A total of 2,306 patients were
randomised in both trials, including former and current smokers,
and patients across all blood eosinophil counts and all stages of
lung function severity.18,19 Patients
were placed on a regimen of tozorakimab 300mg once every four
weeks, or placebo over the course of 52 weeks on top of inhaled
therapy.
Prior to enrolment, patients received standard of care inhaled
maintenance therapy for at least three months. The primary endpoint
is annualised rate of moderate-to-severe COPD exacerbations in
former smokers with COPD. A key secondary endpoint measured the
annualised rate of moderate-to-severe COPD exacerbations in the
overall population of former and current
smokers.18,19
MIRANDA
MIRANDA is a Phase III double-blind, placebo-controlled trial
investigating the efficacy and safety of tozorakimab in adults with
symptomatic COPD with a history of ≥2 moderate or ≥1
severe COPD exacerbations in the 12 months prior to enrolment. A
total of 1,454 patients were randomised in this trial, including
former and current smokers, and patients across all blood
eosinophil counts and all stages of lung function
severity.1 Patients
were placed on a regimen of tozorakimab 300mg once every two weeks,
or placebo over the course of 52 weeks on top of inhaled
therapy.
Prior to enrolment, patients received standard of care inhaled
maintenance therapy for at least three months. The primary endpoint
is annualised rate of moderate-to-severe COPD exacerbations in
former smokers with COPD. A key secondary endpoint measured
the annualised rate of moderate-to-severe COPD exacerbations in the
overall population of former and current
smokers.1
PROSPERO
The PROSPERO trial is a randomised, long-term extension clinical
trial that enrolled patients who completed the OBERON or TITANIA
trials. PROSPERO has a different primary endpoint, which is the
annualised rate of only severe COPD exacerbations (hospitalisations
and death) in former smokers with COPD over 104 weeks. A total of
1,713 patients were randomised in this trial.20
Tozorakimab
Tozorakimab is being developed by AstraZeneca as a first-in-class
potent human immunoglobulin monoclonal antibody that binds to
interleukin (IL-33). Tozorakimab targets the top of the
inflammatory cascade uniquely inhibiting IL-33 signalling in two
ways, thereby suppressing inflammation and disrupting the cycle of
mucus dysfunction.8 Tozorakimab
is currently being investigated in a Phase III clinical trial for
severe viral lower respiratory tract disease and a Phase II trial
for asthma.12,13 Tozorakimab was
granted Fast Track Designation by the US Food and Drug
Administration for the treatment of severe viral lower respiratory
tract disease in November 2023 and for COPD in December
2024.21
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/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Diseases, and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca's innovative
medicines are sold in more than 125 countries and used by millions
of patients worldwide. Please visit astrazeneca.com and
follow the Company on Social Media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1.
Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in
Symptomatic Chronic Obstructive Pulmonary Disease With a
History of Exacerbations (MIRANDA). [Online]. Available
at: https://clinicaltrials.gov/study/NCT06040086. [Last accessed:
April 2026]
2. Montes de Oca M, Perez-Padilla
R, Celli B, et al. The global burden of COPD: epidemiology and
effect of prevention strategies. Global Epidemiology of Chronic
Respiratory Disease. 2025;
13(18):709-724.
3.
World Health Organization (WHO). The top 10 causes of death. 2024.
Available at:
https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
[Last accessed: April 2026]
4. Chen S, Small M, Lindner L, Xu X.
Symptomatic burden of COPD for patients receiving dual or triple
therapy. Int J Chron
Obstruct Pulmon Dis 2018;13:1365-1376.
5. Chen S, Miravitlles M,
Rhee CK, et al. Patients with chronic obstructive pulmonary disease
and evidence of eosinophilic inflammation experience exacerbations
despite receiving maximal inhaled maintenance
therapy. Int J Chron
Obstruct Pulmon Dis 2022;17:2187-2200.
6. Nordon C, Carstens
D, Fageras M, et al. Exacerbation and mortality in
COPD patients on triple inhaler and at high exacerbation
risk. Eur Respir
J 2024;64(Suppl.
68):PA1287 (Abstract).
7. Singh D, Han MK, Hawkins NM, et al.
Implications of cardiopulmonary risk for the management of COPD: a
narrative review. Adv Ther. 2024;41:2151-2167.
8. England E, Rees DG, Scott IC, et
al. Tozorakimab (MEDI3506): an anti-IL-33 antibody that
inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce
inflammation and epithelial dysfunction. Sci
Rep. 2023;13:9825.
9. Singh D, Guller P, Reid F, et al. A
Phase 2a trial of the IL-33 mAb tozorakimab in patients with COPD:
FRONTIER-4. Eur Respir
J 2025;doi
10.1183/13993003.02231-2024.
10. Strickson S, Houslay KF, Negri VA, et
al. Oxidised IL-33 drives COPD epithelial pathogenesis via
ST2-independent RAGE/EGFR signalling
complex. Eur Respir
J 2023;62:2202210.
11.
Strickson S, et al. Distinct Pharmacological Profiles of IL-33
Antibodies. [Poster Presentation]. Presented at the American
Thoracic Society (ATS) 2024. May 2024.
12.
Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in Patients
Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen
(TILIA). [Online]. Available at:
https://clinicaltrials.gov/study/NCT05624450 [Last accessed: April
2026]
13.
Clinicaltrials.gov Dose Range Finding Study to Assess Efficacy and
Safety of Tozorakimab in Adults With Uncontrolled Asthma on
Medium-to-High Dose Inhaled Corticosteroids (UMBRIEL). [Online].
Available at: https://clinicaltrials.gov/study/NCT06932263 [Last
accessed: April 2026]
14. Jackson D, Akuthota P, Roufosse F.
Eosinophils and eosinophilic immune dysfunction in health and
disease. Eur Respir
Rev 2022
31(163):210150.
15.
GOLD. Global Strategy for the Diagnosis, Management, and Prevention
of Chronic Obstructive Pulmonary Disease: 2026 Report. Available
at: https://goldcopd.org/2026-gold-report-and-pocket-guide/ [Last
accessed: April 2026]
16.
American Lung Association. COPD Trends Brief: Burden. Available at:
https://www.lung.org/research/trends-in-lung-disease/copd-trends-brief/copd-burden
[Last accessed: April 2026]
17. Suissa S, Dell'Aniello S, Ernst P.
Long-term natural history of chronic obstructive pulmonary disease:
severe exacerbations and mortality. Thorax 2012;67:957-963.
18.
Clinicaltrials.gov. Efficacy and Safety
of Tozorakimab in Symptomatic Chronic Obstructive
Pulmonary Disease With a History of Exacerbations
(OBERON). Available at:
https://clinicaltrials.gov/study/NCT05166889. [Last accessed: April
2026]
19.
Clinicaltrials.gov. Efficacy and Safety
of Tozorakimab in Symptomatic Chronic Obstructive
Pulmonary Disease With a History of Exacerbations.
(TITANIA). [Online]. Available at:
https://clinicaltrials.gov/study/NCT05158387. [Last accessed: April
2026]
20.
Clinicaltrials.gov. Long-term Efficacy and Safety
of Tozorakimab in Participants With Chronic
Obstructive Pulmonary Disease With a History of
Exacerbations (PROSPERO). [Online]. Available at:
https://clinicaltrials.gov/study/NCT05742802 [Last accessed: April
2026]
21.
AstraZeneca. Clinical Trials Appendix Q3 2025 Results Update.
Available from:
https://www.astrazeneca.com/content/dam/az/PDF/2025/9m-q3/9M-and-Q3-2025-results-clinical-trials-appendix.pdf
[Last accessed: April 2026]
Matthew Bowden
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
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AstraZeneca
PLC
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Date: 20 April 2026
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By: /s/
Matthew Bowden
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Name:
Matthew Bowden
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Title:
Company Secretary
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