REG - AstraZeneca PLC - Third tozorakimab positive Phase III in COPD

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RNS Number : 0175B  AstraZeneca PLC  20 April 2026

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
(https://www.astrazeneca.com/media-centre/press-releases/2026/tozorakimab-met-primary-endpoint-in-oberon-titania-phase-iii-trials-in-patients-with-copd.html)
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 3(rd) 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 (https://www.astrazeneca.com/)

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 (http://www.astrazeneca.com/) and follow the
Company on Social Media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

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

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