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 March 2026
Commission
File Number: 001-11960
AstraZeneca PLC
1
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Tozorakimab met OBERON/TITANIA primary endpoints
This announcement contains inside information
27 March 2026
Tozorakimab met primary endpoint in both OBERON and TITANIA Phase
III trials in patients with COPD
First-ever IL-33-targeting biologic to demonstrate statistically
significant and highly clinically meaningful reductions in COPD
exacerbations in two replicate Phase III clinical
trials
Positive high-level results from the Phase III OBERON and TITANIA
trials in patients with chronic obstructive pulmonary disease
(COPD) showed that tozorakimab reduced the annualised rate of
moderate-to-severe COPD exacerbations compared with placebo, 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. Tozorakimab
was generally well tolerated with a favourable safety
profile.
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.1-4 In
the OBERON
and TITANIA trials, tozorakimab was studied in patients with
COPD still
experiencing exacerbations while on inhaled standard of
care.5,6 Patients
received tozorakimab 300mg or placebo on top of standard of care
once every four weeks.
Nearly 400 million people are diagnosed with COPD, a heterogenous
and progressive disease and the 3rd leading
cause of death globally.7,8 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.9-12
Frank Sciurba, MD, FCCP, Professor of Pulmonary and Critical Care
Medicine, University of Pittsburgh, Chief Investigator of LUNA
programme, said: "These
trial results suggest that targeting the IL-33 pathway with
tozorakimab delivers meaningful clinical benefit in a trial
representing a broad COPD population, independent of smoking status
and eosinophilic levels. COPD has long been a difficult-to-treat
disease with inherent heterogeneity and significant unmet need,
with up to half of patients worldwide at risk of exacerbations,
hospitalisations, cardiopulmonary events, and death - underscoring
the importance of these results for advancing COPD
science."
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D,
AstraZeneca, said: "Today's tozorakimab results deliver the first
two confirmatory Phase III trials for an IL-33 biologic, which is a
major scientific advancement in COPD, the world's third leading
cause of death. Tozorakimab works in a fundamentally different way
from other biologics, inhibiting the signalling of the reduced and
oxidised forms of IL-33 to both decrease inflammation and disrupt
the cycle of mucus dysfunction that are key disease drivers in
COPD."
The full results from the OBERON and TITANIA clinical trials will
be shared with the scientific community at an upcoming medical
meeting.
Additional Phase III trials of tozorakimab in COPD, PROSPERO and
MIRANDA, are ongoing.13,14 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.15,16
*eosinophil: a
type of white blood cell, which at increased levels may contribute
to inflammation in respiratory diseases.17
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.8,18 Common
symptoms include breathlessness, chronic cough and excess mucus
production.18 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.18 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.12,18 In
the US, exacerbations cause more than 2,500 emergency department
visits per day.19 Only
50% of COPD patients live more than 3.5 years after their first
severe exacerbation.20
Phase III LUNA programme
Tozorakimab's Phase III COPD development programme includes four
clinical trials: OBERON, TITANIA, PROSPERO and
MIRANDA.
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 irrespective of blood eosinophil count or
smoking status and across all stages of lung function
severity.5,6 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.5,6
PROSPERO
The PROSPERO trial is a randomised, long-term extension clinical
trial that enrolled patients who completed the OBERON or TITANIA
trials. The primary endpoint is the annualised rate of severe COPD
exacerbations in former smokers with COPD over 104 weeks. A total
of 1,713 patients were randomised in this trial.13 Results
are expected in H1 2026.
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, recruited
irrespective of blood eosinophil count or smoking status
and across
all stages of lung function severity.14 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. Key
secondary endpoints include the annualised rate of
moderate-to-severe COPD exacerbations in the overall population of
former and current smokers.14 Results
are expected in H1 2026.
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.1 Tozorakimab
is currently being investigated in Phase III clinical trials for
COPD and severe viral lower respiratory tract disease and a Phase
II trial for asthma.5,6,13-16 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
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References
1. 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.
2. 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.
3. 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.
4.
Strickson S, et al. Distinct Pharmacological Profiles of IL-33
Antibodies. [Poster Presentation]. Presented at the American
Thoracic Society (ATS) 2024. May 2024.
5.
Clinicaltrials.gov. Efficacy and Safety
of Tozorakimab in Symptomatic Chronic Obstructive
Pulmonary Disease With a History of Exacerbations
(OBERON). [Online]. Available at:
https://clinicaltrials.gov/study/NCT05166889. Accessed March 2026.
6.
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. Accessed March
2026.
7. 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.
8.
World Health Organization (WHO). The top 10 causes of death. 2024.
Available from:
https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death
Accessed March 2026.
9. 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.
10. 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.
11. 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).
12. 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.
13.
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. Accessed March
2026.
14.
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. Accessed March
2026.
15.
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 Accessed March
2026.
16.
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 Accessed
March 2026.
17. Jackson D, Akuthota P, Roufosse F,
Eosinophils and eosinophilic immune dysfunction in health and
disease. Eur Respir
Rev 2022
31(163):210150.
18.
GOLD. Global Strategy for the Diagnosis, Management, and Prevention
of Chronic Obstructive Pulmonary Disease: 2026 Report. Available
from: https://goldcopd.org/2026-gold-report-and-pocket-guide/
Accessed March 2026.
19.
American Lung Association. COPD Trends Brief: Burden. Available
from:
https://www.lung.org/research/trends-in-lung-disease/copd-trends-brief/copd-burden
Accessed March 2026.
20. 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.
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
Accessed March 2026.
Matthew Bowden
Company Secretary
AstraZeneca PLC
This announcement contains information that AstraZeneca PLC is
obliged to make public pursuant to the EU Market Abuse Regulation
(596/2014) and the assimilated EU Market Abuse Regulation
(596/2014) as it forms part of the law of the United Kingdom by
operation of the European Union (Withdrawal) Act 2018. This
announcement was submitted for publication, through the agency of
the contact person(s) set out above, at 7:00 GMT on 27 March
2026.
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: 27 March 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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