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 October 2022
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.
Update on MESSINA Phase III trial
25
October 2022 07:00 BST
Update on the MESSINA Phase III trial for Fasenra in eosinophilic
esophagitis
MESSINA did
not meet one
of the two dual-primary endpoints, demonstrating a
statistically significant
improvement in histological
disease remission with Fasenra, but not in dysphagia symptoms,
compared to placebo
Eosinophilic esophagitis (EoE) is a rare,
progressive, chronic inflammatory disease of the esophagus
currently believed to be characterised by
the abnormal presence of eosinophils, a type of white blood cell,
in the inner lining of the esophagus.1-3 Patients
experience difficulty with swallowing (dysphagia), pain, food
getting stuck and anxiety.4,5
High-level results from the MESSINA Phase III
trial showed that AstraZeneca's Fasenra (benralizumab) did not meet one of the two
dual-primary endpoints. Fasenra demonstrated a statistically significant
improvement in histological disease remission, but not a change in
dysphagia symptoms, compared to placebo, in patients with EoE aged
12 years or older.
Mene Pangalos, Executive Vice President,
BioPharmaceuticals R&D, AstraZeneca said: "The results from the
MESSINA Phase III trial in eosinophilic esophagitis confirm
that Fasenra achieved
near complete depletion
of tissue eosinophils, consistent with its mechanism of
action, however
this did not translate into an improvement in dysphagia
symptoms. We will continue to analyse the complete data set to
share with the scientific community."
In the trial, histological disease remission was
measured as the proportion of patients with less than or equal to
six eosinophils per high power field at Week 24. Burden of
dysphagia was assessed using the patient-reported Dysphagia Symptom
Questionnaire (DSQ) and measured as a mean change from baseline at
Week 24. The trial included 210 patients, who received
either Fasenra or placebo at four-week
intervals.
The safety and tolerability profile
for Fasenra in the trial was consistent with the known
profile of the medicine.
Results
from MESSINA will be presented at an upcoming medical
meeting.
Fasenra is
currently approved as an add-on maintenance treatment for severe
eosinophilic asthma in the US, EU, Japan and other
countries,6 and
is approved for self-administration in the US,6 EU7 and
other countries.
Notes
MESSINA
MESSINA is a randomised, placebo-controlled,
double-blind, parallel-group, multicentre, global Phase III trial
designed to investigate the efficacy and safety
of Fasenra compared to placebo in patients aged 12 to
65 years of age with symptomatic and histologically active
EoE.8,9
The dual-primary endpoints analysed at Week 24
were the proportion of patients with a histologic response, defined
as a peak esophageal eosinophil count less than or equal to 6
eosinophils per high power field, and mean changes from baseline in
Dysphagia Symptom Questionnaire (DSQ).8 The
peak eosinophil count is obtained when a biopsy of the tissue of
the esophagus is examined under a microscope. The histologic
response endpoint used in the trial is consistent with histologic
remission.10 The
DSQ captures the presence and severity of dysphagia symptoms in the
past day in a 4-item patient-reported questionnaire and the score
is calculated over 14-day periods, ranging from 0 to 84, with a
lower score indicating less severe dysphagia.8
The trial period consists of a 24-week
double-blind, placebo-controlled treatment period followed by a
28-week open-label treatment period.8 Eligible
patients were randomised in a 1:1 ratio to receive either 30 mg
of Fasenra or placebo at 4-week intervals for the
double-blind period. Patients who complete the double-blind period
on Fasenra continue into the open-label treatment
period with all patients receiving Fasenra 30 mg at 4-week intervals until Week 52,
with a further open-label extension offered to eligible patients
thereafter.9
In the trial, patients were allowed to remain on
background medications for EoE, including proton pump inhibitors,
topical corticosteroids, and EoE-driven diet elimination, provided
that they were stable prior to entry and during the first 52 weeks
of treatment, unless changes were clinically
indicated.8,9
Fasenra
Fasenra (benralizumab) is a monoclonal antibody that
binds directly to IL-5 receptor alpha on eosinophils and attracts
natural killer cells to induce rapid and near-complete depletion of
blood and tissue eosinophils in most patients via apoptosis
(programmed cell death).11
Fasenra is
currently approved as an add-on maintenance treatment for severe
eosinophilic asthma in the US, EU, Japan and other
countries,6 and
is approved for self-administration in the US,6 EU7 and
other countries. Fasenra has
been studied in almost 4,000 patients in global clinical
trials.12-16
Fasenra is
in development for other eosinophilic diseases including bullous
pemphigoid, chronic obstructive pulmonary disease, chronic
rhinosinusitis with nasal polyps, chronic spontaneous urticaria,
eosinophilic esophagitis, eosinophilic gastritis/eosinophilic
gastroenteritis, eosinophilic granulomatosis with polyangiitis,
hypereosinophilic syndrome and non-cystic fibrosis
bronchiectasis.
Fasenra was
developed by AstraZeneca and is in-licensed from BioWa, Inc., a
wholly-owned subsidiary of Kyowa Kirin Co., Ltd.,
Japan.
AstraZeneca in Respiratory and Immunology
Respiratory
& Immunology, part of BioPharmaceuticals, is one of
AstraZeneca's main disease areas and is a key growth driver for the
Company.
AstraZeneca
is an established leader in respiratory care with a 50-year
heritage. The Company aims to transform the treatment of asthma and
COPD by focusing on earlier biology-led treatment, eliminating
preventable asthma attacks, and removing COPD as a top-three
leading cause of death. The Company's early respiratory research is
focused on emerging science involving immune mechanisms, lung
damage and abnormal cell-repair processes in disease and neuronal
dysfunction.
With
common pathways and underlying disease drivers across respiratory
and immunology, AstraZeneca is following the science from chronic
lung diseases to immunology-driven disease areas. The Company's
growing presence in immunology is focused on five mid- to
late-stage franchises with multi-disease potential, in areas
including rheumatology (including systemic lupus erythematosus),
dermatology, gastroenterology, and systemic eosinophilic-driven
diseases. AstraZeneca's ambition in Respiratory & Immunology is
to achieve disease modification and durable remission for millions
of patients worldwide.
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 operates in
over 100 countries and its innovative medicines are used by
millions of patients worldwide. Please
visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca
Contacts
For details on how to contact the Investor
Relations Team, please click here.
For Media contacts, click here.
References
1. Muir A, et al. Eosinophilic
Esophagitis: A Review. JAMA. 2021;326:1310-1318.
2. Dellon ES, et al. Epidemiology and
Natural History of Eosinophilic
Esophagitis. Gastroenterology.
2018;154:319-332.e3.
3. Cheng E, et al. Tissue remodeling
in eosinophilic esophagitis. Am J Physiol Gastrointest
Liver Physiol. 2012;303:G1175-G1187.
4. Hirano I, et al. Clinical
Implications and Pathogenesis of Esophageal Remodeling in
Eosinophilic Esophagitis. Gastroenterol Clin North
Am. 2014;43:297-316.
5. Lucendo AJ, et al. Guidelines on
eosinophilic esophagitis: evidence-based statements and
recommendations for diagnosis and management in children and
adults. United European Gastroenterol
J.
2017;5:335-358.
6. AstraZeneca news
release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-approved-in-the-us-for-self-administration-in-a-new-pre-filled-auto-injector-the-fasenra-pen-04102019.html [Last
accessed: October 2022].
7. AstraZeneca news
release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-receives-positive-eu-chmp-opinion-for-self-administration-and-the-new-fasenra-pen-a-pre-filled-single-use-auto-injector-01072019.html [Last
accessed: October 2022].
8.
Clinicaltrials.gov. A Study of Benralizumab in Patients With
Eosinophilic Esophagitis (MESSINA). [Online] Available
at: https://www.clinicaltrials.gov/ct2/show/NCT04543409 [Last
accessed: October 2022].
9. AstraZeneca Data
on file. 2022 - REF-162311.
10. U.S. Department of
Health and Human Services, Food and Drug Administration, Center for
Drug Evaluation and Research (CDER). Eosinophilic Esophagitis:
Developing Drugs for Treatment. Guidance for Industry. 2020.
Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/eosinophilic-esophagitis-developing-drugs-treatment-guidance-industry [Last
accessed: October 2022].
11.
AstraZeneca. Fasenra Summary
of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/fasenra-epar-product-information_en.pdf [Last
accessed: October 2022].
12. Bleecker ER, et al. Efficacy and safety
of benralizumab for patients with severe asthma uncontrolled with
high-dosage inhaled corticosteroids and long-acting b 2-agonists
(SIROCCO): a randomised, multicentre, placebo-controlled phase 3
trial. Lancet. 2016;388:2115-2127.
13. FitzGerald JM, et al. Benralizumab, an
anti-interleukin-5 receptor a monoclonal antibody, as add-on
treatment for patients with severe, uncontrolled, eosinophilic
asthma (CALIMA): a randomised, double-blind, placebo-controlled
phase 3 trial. Lancet. 2016;388:2128-2141.
14. Nair P, et al. Oral
Glucocorticoid-Sparing Effect of Benralizumab in Severe
Asthma. N Engl J
Med. 2017;376:2448-2458.
15. Menzies-Gow A, et al. Oral
corticosteroid elimination via a personalised reduction algorithm
in adults with severe, eosinophilic asthma treated with
benralizumab (PONENTE): a multicentre, open-label, single-arm
study. Lancet Respir
Med.
2022;10:47-58.
16. Harrison TW, et al. Onset of effect and
impact on health-related quality of life, exacerbation rate, lung
function, and nasal polyposis symptoms for patients with severe
eosinophilic asthma treated with benralizumab (ANDHI): a
randomised, controlled, phase 3b trial. Lancet Respir
Med. 2021;9:260-274.
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.
Date:
25 October 2022
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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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