TIDMAZN
RNS Number : 9492D
AstraZeneca PLC
25 October 2022
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)
EU(7) 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)
EU(7) 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
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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 <BETA> 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 <ALPHA> 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
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