阿斯利康Tezspire治疗嗜酸性食管炎III期CROSSING试验达到全部主要终点

----- a4036s.htm -----
6-K
1
a4036s.htm
TEZSPIRE CROSSING TRIAL MET PRIMARY ENDPOINTS
a4036s
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 August 2026
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Tezspire CROSSING trial met primary endpoints
27 August
2026
Tezspire
demonstrates positive Phase III results in
eosinophilic esophagitis across both co-primary and all key
secondary endpoints
Statistically significant and clinically
meaningful disease and symptom improvements compared to
placebo maintained through week 52
Efficacy in a third epithelial-driven inflammatory disease
supports broad potential of Tezspire
Positive high-level results from the Phase III CROSSING trial in
patients with eosinophilic esophagitis (EoE) showed that
AstraZeneca and Amgen’s
Tezspire
(tezepelumab) demonstrated
statistically significant and clinically meaningful improvements
across both co-primary and all key secondary endpoints at week 24,
which were sustained through week 52 in both doses tested. The
co-primary endpoints were histologic remission and the frequency
and severity of dysphagia (difficulty swallowing) compared to
placebo. The safety profile of
Tezspire
in the trial was generally consistent with
its approved indications.
CROSSING is a randomised, double-blind trial that evaluated the
efficacy and safety of
Tezspire
administered
subcutaneously every four weeks compared to placebo in adults and
adolescents with symptomatic and uncontrolled EoE while on
maintenance therapy.
1
In
the trial, the first co-primary endpoint, histologic remission, was
defined as having a low count of peak eosinophils in the esophageal
tissue.
1
The
second co-primary endpoint, the frequency and severity of
dysphagia, was assessed using the patient-reported Dysphagia
Symptom Questionnaire (DSQ) and measured as a mean change from
baseline in DSQ score.
1
EoE is a chronic and progressive epithelial-driven inflammatory
disorder of the esophagus affecting more than 470,000 people in the
US, with the prevalence increasing five-fold since
2009.
2,3
The
inflammation of the esophagus can lead to dysphagia, food impaction
and esophageal narrowing.
2
Nearly
half of patients, including adolescents, do not achieve adequate
disease control with current first-line treatments, which include
dietary restriction, swallowed topical corticosteroids and proton
pump inhibitors.
4-6
For
patients, the risk of food moving slowly or becoming stuck can make
daily meals difficult and stressful.
7
Arjan Bredenoord, MD, Gastroenterologist and professor at the
Amsterdam University Medical Center, Amsterdam, The
Netherlands, and primary investigator in the trial, said:
“Despite the availability of first-line therapies or
dietary interventions, many patients with eosinophilic esophagitis
still experience substantial burden, including difficulty
swallowing food, and emotional and daily-life impacts of the
disease. The impressive results from the CROSSING trial sustained
over 52 weeks demonstrate that tezepelumab, taken every four
weeks, could provide a new approach to treating this disease,
with the potential to help more patients achieve remission and
symptom improvement.”
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D
said: “The positive results of the Phase III CROSSING trial
reinforce our confidence in the differentiated mechanism of action
of
Tezspire,
which
has now demonstrated clinically meaningful efficacy in a third
epithelial-driven inflammatory disease. Epithelial science
represents an important and rapidly evolving area in respiratory
and immunology medicine, and we look forward to sharing these
results at an upcoming medical meeting and with regulatory
authorities as quickly as
possible.”
Full results will be shared with regulatory authorities and the
scientific community at an upcoming medical meeting.
Tezspire
is a
first-in-class human monoclonal antibody that inhibits the action
of thymic stromal lymphopoietin (TSLP), a key epithelial cytokine
that sits at the top of multiple inflammatory
cascades.
Tezspire
is currently approved for the treatment of
severe asthma in the US, EU, China, Japan and more than 70
countries across the globe, and for the treatment of chronic
rhinosinusitis with nasal polyps (CRSwNP) in the US, EU, China and
Japan. The Phase III JOURNEY and EMBARK trials
evaluating
Tezspire
in chronic obstructive pulmonary disease
(COPD) are ongoing.
8,9
​
Notes
Eosinophilic Esophagitis (EoE)
EoE is a chronic and progressive epithelial-driven inflammatory
disorder of the esophagus with prevalence growing across the
world.
2,3
It
is characterised by inflammation, remodelling and esophageal
epithelial dysfunction.
2
Epithelial
dysfunction and inflammation are important characteristics of EoE
and impede the ability of the epithelium to act as a physical and
immunological barrier against the external
environment.
2
The most common symptoms of EoE include difficulty and pain when
swallowing, food becoming stuck in the esophagus (which may
require emergency medical interventions), nausea and vomiting,
abdominal or chest pain, poor appetite and difficulty
sleeping.
2,10,11
Many
patients, including adolescents, experience a substantial impact on
their quality of life including significant anxiety related to
swallowing and choking, depression, and decreased work/school
productivity.
12,13
Patients are often treated with proton pump inhibitors or swallowed
topical corticosteroids to manage inflammation.
2,4
Nearly
half of patients with EoE will not respond to standard first-line
therapies or dietary treatment.
5,6
Existing
treatment options, including those targeting downstream mediators,
may not fully address epithelial-driven
inflammation.
14,15
CROSSING
CROSSING is a randomised, double-blind, placebo-controlled,
multi-centre, parallel-group, Phase III trial designed to evaluate
the efficacy and safety of
Tezspire
administered subcutaneously every four
weeks, compared to placebo in patients aged 12-80 years with
symptomatic and histologically active EoE.
1
A
total of 368 patients were randomised in a 1:1:1 ratio to receive
either a low or high dose of
Tezspire
or placebo.
1
The co-primary endpoints analysed at Week 24 were the proportion of
patients with histologic remission, defined as a peak
esophageal eosinophil count less than or equal to six eosinophils
per high-power field, and mean changes from baseline in the
DSQ.
1
The
peak eosinophil count is obtained when biopsies of the tissue of
the esophagus are examined under a microscope.
1
A
count of 15 or more peak eosinophils per high power microscopic
field measured by esophageal biopsy is often the cutoff used to
diagnose EoE.
16,17
The
DSQ captures the presence and severity of dysphagia symptoms in a
daily diary with a four-item patient-reported questionnaire; the
score is calculated over 14-day periods, ranging from zero to 84,
with a higher score indicating more severe
dysphagia.
1
Key secondary endpoints assessed histologic remission and dysphagia
symptoms at Week 52; changes in endoscopic disease features
(EoE-EREFS) and histologic severity and extent (EoE-HSS) at Weeks
24 and 52; as well as endoscopic response, inflammatory remission
and total endoscopic remission at Week 52.
1
In the trial, patients were allowed to remain on background
medications for EoE, including proton pump inhibitors and swallowed
topical corticosteroids, provided that they were stable prior to
entry and during the treatment period.
1
Tezepelumab and TSLP
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.
18
TSLP
is critical in the initiation and persistence of allergic,
eosinophilic and other types of epithelial-driven inflammation
associated with severe asthma, CRSwNP, COPD and
EoE.
19-20
TSLP is released by the epithelium in response to environmental
triggers.
18
Across
these disease states, the expression of TSLP is increased and
correlates with disease severity.
18-22
Tezspire
is approved as a
single-use pre-filled syringe and auto-injector for
self-administration in the US, EU, China and
Japan.
Since
2021, more than 100,000 patients have been treated
with
Tezspire
for severe asthma.
23
In October 2021,
Tezspire
was
granted Orphan Drug Designation by the U.S. Food and Drug
Administration (FDA) for the treatment of EoE.
24
Beyond
EoE,
Tezspire
is
also being explored in Phase III trials in COPD.
8,9
Amgen Collaboration
The 2012 Collaboration Agreement between Amgen and AstraZeneca has
been amended and updated over time. For
Tezspire
, both companies 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 agreement, Amgen and AstraZeneca jointly
commercialise
Tezspire
in the US. Amgen records product sales in
the US, with AZ recording its share of US profits as Alliance
Revenue. Outside of the US, AstraZeneca records product sales.
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 Disease, 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
Tezepelumab in Patients With Eosinophilic Esophagitis (CROSSING).
Available at:
https://clinicaltrials.gov/study/NCT05583227
.
[Last accessed August 2026].
2.
Biedermann L. & Straumann A. Mechanisms and
clinical management of eosinophilic oesophagitis: an
overview.
Nature Reviews Gastroenterol
& Hepatol.
2023;20(2):101-119.
3.
Thel HL, et al. Prevalence and costs of
eosinophilic esophagitis in the United
States.
Clin Gastroenterol
Hepatol.
2025;23(2):272-280.e8.
4.
Hirano I, et al. AGA Institute and the Joint Task
Force on Allergy-Immunology Practice Parameters clinical guidelines
for the management of eosinophilic
esophagitis.
Gastroenterology
.
2020;158(6):1776-1786.
5.
Strauss AL, Falk GW. Refractory eosinophilic
esophagitis: what to do when the patient has not responded to
proton pump inhibitors, steroids and diet.
Curr Opin
Gastroenterol
.
2022;38(4):395-401.
6.
Lucendo AJ, et al. Efficacy of proton pump
inhibitor drugs for inducing clinical and histologic remission in
patients with symptomatic esophageal eosinophilia: a systematic
review and meta-analysis.
Clin Gastroenterol
Hepatol
.
2016; 14(1):13-22.e1.
7.
Ho CN, et al. Patient experience with eosinophilic
esophagitis symptoms and impacts on daily life based on in-trial
qualitative interviews.
J Patient Rep
Outcomes
.
2025;9(1):3.
8.
ClinicalTrials.gov. A Study to Investigate
the Efficacy and Safety of Tezepelumab in Adult Participants With
Moderate to Very Severe COPD (D5241C00007) (JOURNEY). Available
at:
https://clinicaltrials.gov/study/NCT06878261
.
[Last accessed August 2026].
9.
ClinicalTrials.gov. A Study to Investigate
the Efficacy and Safety of Tezepelumab in Adult Participants With
Moderate to Very Severe COPD (D5241C00006) (EMBARK). Available
at:
https://clinicaltrials.gov/study/NCT06883305
.
[Last accessed August 2026].
10.
Gold BD, et al. Health-Related Quality of Life and
Perceived Stigma in Eosinophilic Esophagitis: A Real-World, US,
Web-Based Survey.
Gastro Hep
Adv
.
2024;3(8):1087-97.
11.
MedlinePlus. Eosinophilic esophagitis. Bethesda
(MD): National Library of Medicine (US). Available
at:
https://medlineplus.gov/eosinophilicesophagitis.html
. [Last
accessed August 2026].
12.
Taft TH, et al. Anxiety and depression in
eosinophilic esophagitis: a scoping review and recommendations for
future research.
J Asthma
Allergy
.
2019;12:389–99.
13.
Harris RF, et al. Psychosocial dysfunction in
children and adolescents with eosinophilic
esophagitis.
J Pediatr Gastroenterol
Nutr
.
2013;57:500–5.
14.
Underwood B, et al. Breaking down the complex
pathophysiology of eosinophilic
esophagitis.
Ann Allergy Asthma
Immunol
.
2023;130(1):28-39
15.
Gautam R, et al. Eosinophilic esophagitis:
mechanisms of disease and approach to
treatment.
Curr Allergy Asthma
Rep
.
2026;26:21.
16.
Lucendo AJ, et al. British Society of
Gastroenterology (BSG) and British Society of Paediatric
Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint
consensus guidelines on the diagnosis and management of
eosinophilic oesophagitis in children and
adults.
Gut
. 2022;71(8):1459-1487.
17.
Dellon ES, et al. ACG Clinical Guideline:
Diagnosis and Management of Eosinophilic
Esophagitis.
Am J
Gastroenterol
.
2025;120(1):31-59.
18.
Varricchi G, et al. Thymic Stromal Lymphopoietin
Isoforms, Inflammatory Disorders, and
Cancer.
Front
Immunol
.
2018;9:1595.
19.
Calderon AA, et al. Targeting interleukin-33 and
thymic stromal lymphopoietin pathways for novel pulmonary
therapeutics in asthma and COPD.
Eur Respir
Rev
.
2023;32(167):220144.
20.
Nagarkar DR, et al. Thymic stromal
lymphopoietin activity is increased in nasal polyps of patients
with chronic rhinosinusitis.
J Allergy Clin
Immunol
.
2013;132(3):593-600.e12.
21.
Ying, S, et al. Thymic stromal lymphopoietin
expression is increased in asthmatic airways and correlates with
expression of Th2-attracting chemokines and disease
severity.
J Immunol
2005;174:8183-8190.
22.
Sherrill JD, et al. Preferential Secretion of
Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated
Esophageal Epithelial Cells: Relevance to Eosinophilic
Esophagitis.
PLoS One
. 2016;11(2): e0148216.
23.
AstraZeneca
Data on File. 2025. REF-278452.
24.
AstraZeneca press release. Tezepelumab granted
Orphan Drug Designation in the US for eosinophilic esophagitis.
Available at:
https://www.astrazeneca.com/media-centre/press-releases/2021/tezepelumab-granted-orphan-drug-designation-in-the-us-for-eosinophilic-esophagitis.html
.
[Last accessed: August 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.
AstraZeneca
PLC
Date:
27 August 2026
By: /s/
Matthew Bowden
Name:
Matthew Bowden
Title:
Company Secretary