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 November 2024
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Tezspire nasal polyps trial met primary endpoints
08 November 2024
Tezspire met both
co-primary endpoints in the Phase III WAYPOINT trial in patients
with chronic rhinosinusitis with nasal polyps
Tezspire demonstrated a statistically significant and clinically
meaningful reduction in nasal polyp size and reduced nasal
congestion compared to placebo
Positive high-level results from the Phase III WAYPOINT trial in
patients with chronic rhinosinusitis with nasal polyps (CRSwNP
[nasal polyps]) showed that AstraZeneca and
Amgen's Tezspire (tezepelumab) demonstrated a statistically
significant and clinically meaningful reduction in the size of
nasal polyps and reduced nasal congestion compared to
placebo.
WAYPOINT is a randomised, double-blind trial that evaluated the
efficacy and safety of Tezspire administered
subcutaneously compared to placebo in adults with
severe CRSwNP.
Participants in the trial were symptomatic despite treatment with
standard of care (intranasal corticosteroids
[INCS]).1
Dr. Joseph Han, Vice Chair of Rhinology & Endoscopic Sinus and
Skull Base Surgery, and Allergy, Otolaryngology-Head and Neck
Surgery, Eastern Virginia Medical School, US, and co-primary
investigator in the trial, said, "Chronic rhinosinusitis with nasal
polyps negatively impact patients' daily lives with obstructions
leading to disturbances in smell, taste and sleep as well as pain
and fatigue. The impressive data from the WAYPOINT trial
demonstrate tezepelumab's potential as a new treatment for patients
whose lives are disrupted by this debilitating
disease."
Dr. Brian Lipworth, Professor of Allergy and Pulmonology, Scottish
Centre for Respiratory Research, and Tayside Rhinology Ear,
Nose and Throat Clinic, Ninewells Hospital University of Dundee in
Scotland, UK, and co-primary investigator in the trial, said,
"Patients diagnosed with nasal polyps continue to experience
significant burden including repeat surgeries and frequent
treatment with high doses of oral corticosteroids, which are
associated with serious systemic side effects. The tezepelumab data
are clinically meaningful and offer patients with nasal polyps hope
for a potential new treatment option that may reduce the burden on
patients and healthcare systems."
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D
said: "We are excited by the positive results from the Phase III
WAYPOINT trial, which show that patients with nasal polyps strongly
benefitted from treatment with tezepelumab. These results reinforce
that tezepelumab's first-in-class mode of action, targeting TSLP at
the top of the inflammatory cascade, effectively addresses the
multiple drivers of epithelial-driven inflammatory
diseases."
The safety profile and tolerability of Tezspire in this trial were consistent with the known
profile of the medicine.
Full
results will be shared with regulatory authorities
and the scientific
community at an upcoming medical meeting.
Tezspire is currently
approved for the treatment of severe asthma in the US, EU, Japan,
and nearly 60 countries across the globe.2-5 It
is approved as a single-use pre-filled syringe and
auto-injector for self-administration in the US and
EU.2,3
+++
Notes:
Chronic Rhinosinusitis with Nasal Polyps (CRSwNP (nasal
polyps))
CRSwNP is a complex inflammatory disorder, characterised by
persistent inflammation of the nasal mucosa accompanied by benign
growths, called nasal polyps.6,7 Nasal
polyps can block nasal passages and lead to breathing problems,
difficulty in sense of smell, nasal discharge, facial pain, sleep
disturbance and other adverse effects on quality of
life.8-10
Epithelial dysfunction and inflammation are important
characteristics of chronic
rhinosinusitis and impede the ability of the epithelium to act
as a physical and immunological barrier against the external
environment.11 Thymic
stromal lymphopoietin (TSLP) is an epithelial cytokine that has
been implicated in shared pathophysiological processes underlying
severe asthma and CRSwNP.10,12
Current treatments for CRSwNP include intranasal and/or
systemic corticosteroids, surgery and biologics.8,13-16
Phase III WAYPOINT trial
WAYPOINT is a double-blind, multi-centre, randomised,
placebo-controlled, parallel group trial designed to evaluate the
efficacy and safety of tezepelumab in adults with
severe CRSwNP.1 Participants
received tezepelumab or placebo, administered via subcutaneous
injection. The trial also included a post-treatment follow-up
period of 12-24 weeks for participants who completed the 52-week
treatment period.1
The co-primary endpoints of the trial, were change from baseline in
total nasal polyp size, measured by the endoscopic total Nasal
Polyp Score, and change from baseline in bi-weekly mean nasal
congestion, measured by the participant reported Nasal Congestion
Score evaluated as part of the daily Nasal Polyposis Symptom
Diary.1 Key
secondary endpoints included loss of smell; improvement in
disease specific health-related quality of life as measured by
SinoNasal Outcome Test (SNOT-22) score; Lund-Mackay score; time to
surgery decision and/or systemic corticosteroids for nasal
polyposis; time to nasal polyposis surgery decision; time to
systemic corticosteroids for nasal polyposis; Nasal Polyposis
Symptom Diary total symptom score and, in the population with
co-morbid asthma, pre-bronchodilator FEV1 at Week
52.
Tezepelumab
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
endothelial inflammation associated with severe asthma and other
inflammatory diseases.17,18
TSLP is released in response to multiple triggers (including
allergens, viruses and other airborne particles) associated
with asthma,
CRSwNP, chronic obstructive pulmonary disease (COPD), eosinophilic
esophagitis (EoE) and other diseases.18,19 Expression
of TSLP is increased in these patients and has been correlated with
disease severity.10,17 Blocking
TSLP may prevent the release of pro-inflammatory cytokines by
immune cells, resulting in the prevention of exacerbations and
improved disease control.17,18,20 Tezepelumab
acts at the top of the inflammatory cascade and research indicates
that targeting TSLP released by the airway epithelium may be a
potential approach to treating diseases of the lower airways in the
future.17,21,22
Tezspire is
approved in the US, the EU and nearly 60 countries for the add-on
maintenance treatment of adult and paediatric patients aged 12
years and older with severe asthma.2-5
Beyond CRSwNP, tezepelumab is also in development for other
potential indications including COPD and EoE.23,24 In
October 2021, tezepelumab was granted Orphan
Drug Designation by
the U.S. Food and Drug Administration (FDA) for the treatment of
EoE. In
July 2024, the U.S. FDA granted a Breakthrough Therapy Designation
for tezepelumab for the add-on maintenance treatment of patients
with moderate to very severe COPD characterised by an eosinophilic
phenotype.
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
commercialise 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.
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/Nasdaq: 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 Tezepelumab in Participants With Severe Chronic
Rhinosinusitis With Nasal Polyposis (WAYPOINT). Available
at: https://clinicaltrials.gov/ct2/show/NCT04851964.
[Last accessed: November 2024].
2.
Tezspire (tezepelumab) US
prescribing information. Available at: https:// www.accessdata.fda.gov/drugsatfda_docs/label/2023/761224s003lbl.pdf.
[Last accessed: November
2024].
3.
Tezspire (tezepelumab) Summary of
Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/tezspire-epar-product-information_en.pdf.
[Last accessed: November 2024].
4.
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: November 2024].
5.
Data
on File. AstraZeneca. 2024. REF-251231.
6.
Bachert C, et al. Phenotypes and Emerging Endotypes of Chronic
Rhinosinusitis. J Allergy Clin Immunol
Pract. 2016; 4 (4):
621-628.
7.
Del Toro E, Portela J. Nasal
Polyps. [Updated
2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL):
StatPearls Publishing; 2024 Jan-. Available
from: https://www.ncbi.nlm.nih.gov/books/NBK560746/ [Last
accessed: November 2024].
8.
Stevens WW, et al. Chronic Rhinosinusitis with Nasal
Polyps. J Allergy Clin Immunol
Pract. 2016; 4 (4):
565-572.
9.
Abdalla S, et al. Prevalence of sinonasal outcome test (SNOT-22)
symptoms in patients undergoing surgery for chronic rhinosinusitis
in the England and Wales National prospective
audit. Clin
Otolaryngol. 2012; 37 (4):
276-282.
10.
Laidlaw TM, et al. Chronic Rhinosinusitis with nasal polyps and
asthma. J Allergy Clin Immunol
Pract 2021;9:1133-1141.
11.
Wynne M, et al. Contribution of epithelial cell dysfunction
to the pathogenesis of chronic rhinosinusitis with nasal
polyps. Am J Rhinol
Allergy.
2019;33:782-790.
12.
Liao B, et al. Interaction of thymic stromal
lymphopoietin, IL-33, and their receptors in epithelial cells in
eosinophilic chronic rhinosinusitis with nasal
polyps. Allergy. 2015;70:1169-1180.
13.
Xolair (omalizumab) Summary of
Product Characteristics; Available at: https://www.ema.europa.eu/en/documents/product-information/xolair-epar-product-information_en.pdf [Last
accessed November 2024].
14.
Xolair (omalizumab) US
prescribing information; Available at: https://www.gene.com/download/pdf/xolair_prescribing.pdf [Last
accessed: November 2024].
15.
Nucala (mepolizumab) US
prescribing information; Available at: https:// www.accessdata.fda.gov/drugsatfda_docs/label/2021/761122s006,125526s018lbl.pdf.
[Last accessed November
2024].
16.
Dupixent (dupilumab) US
prescribing information; Available at: https://www.regeneron.com/downloads/dupixent_fpi.pdf.
[Last accessed: November
2024].
17.
Corren J, et al. Tezepelumab in adults with uncontrolled asthma
. N
Engl J Med.
2017;377:936-946.
18.
Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms,
Inflammatory Disorders, and Cancer. Front
Immunol.
2018;9:1595.
19.
Zhang M, et al. Hypoxia induces the production of
epithelial-derived cytokines in eosinophilic chronic rhinosinusitis
with nasal polyps. Int
Immunopharmacol 2023;121:110559
20.
Li Y, et al. Elevated Expression of IL-33 and TSLP in the
Airways of Human Asthmatics In Vivo: A Potential Biomarker of
Severe Refractory Disease. J Immunol. 2018;200: 2253-2262.
21.
Menzies-Gow A, et al. Tezepelumab in Adults and Adolescents with
Severe, Uncontrolled Asthma. N Engl J
Med.
2021;384:1800-1809.
22.
Laidlaw TM et al. Tezepelumab Efficacy in Patients with Severe,
Uncontrolled Asthma with Comorbid Nasal Polyps in
NAVIGATOR. J Asthma
Allergy. 2023 Sep
4:16:915-932.
23.
Clinicaltrials.gov. Tezepelumab
COPD Exacerbation Study (COURSE) [Online]. Available
at: https://clinicaltrials.gov/ct2/show/NCT04039113.
[Last accessed: November 2024].
24.
Clinicaltrials.gov. Efficacy and
Safety of Tezepelumab in Patients with Eosinophilic Esophagitis
(CROSSING). Available at: https://clinicaltrials.gov/study/NCT05583227?rank=1.
[Last accessed: November 2024].
Adrian Kemp
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:
08 November 2024
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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