a5906e
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 March 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 US review
of Fasenra in nasal polyps
14 March 2022 07:00 GMT
Update on US regulatory review
of Fasenra
in chronic rhinosinusitis with nasal polyps
The US Food and Drug Administration (FDA) has issued a complete
response letter (CRL) regarding the supplemental Biologics License
Application (sBLA) for Fasenra (benralizumab) for patients with
inadequately controlled chronic rhinosinusitis with nasal polyps
(CRSwNP).
The sBLA submitted to the FDA by AstraZeneca included data from the
OSTRO Phase III trial, which met both co-primary endpoints with a
safety profile consistent with the known profile of the
medicine.1 The
CRL requested additional clinical data and the Company is working
closely with the FDA regarding next steps. The Company remains
committed to bringing Fasenra to patients with CRSwNP and a second Phase
III trial, ORCHID,
in this indication is ongoing.2
Fasenra is currently
approved as an add-on maintenance treatment for severe eosinophilic
asthma in the US, EU, Japan and other countries and is approved for
self-administration in the US, EU and other
countries.
The FDA granted Orphan Drug Designation
(ODD) for Fasenra for eosinophilic granulomatosis with
polyangiitis in 2018, and hypereosinophilic syndrome and
eosinophilic esophagitis (EoE) in 2019. In November 2021, the
FDA also granted ODD for Fasenra for eosinophilic gastroenteritis
(EGE) and eosinophilic gastritis (EG), and
a Fast Track
Designation for the
treatment of EG with or without EGE in the
US.
Notes
CRSwNP
CRSwNP is characterised by persistent inflammation of the
mucous membrane lining the nasal passages and sinuses accompanied
by benign growths, called nasal polyps.3,4 Nasal
polyps can block nasal passages and lead to breathing problems,
reduction in the sense of smell, nasal discharge, sleep disturbance
and other adverse effects on quality of life.5-7 Eosinophilic
infiltration of the tissues is thought to play a role in the
disease pathophysiology.4,5
Current treatments for nasal polyps include intranasal
corticosteroids (INCS) or oral corticosteroids and surgery to
remove polyps, but these often provide only short-term relief and
the need for repeated interventions can be high.8,9 Since
2019, other biologic medicines have been approved or recommended to
treat nasal polyps.6,10-12
OSTRO
OSTRO was a randomised, double-blinded, multi-centre,
parallel-group, 56-week Phase III trial to evaluate the efficacy
and safety of Fasenra compared to placebo in patients with nasal
polyposis.1 Fasenra was
evaluated in patients, regardless of blood eosinophil count with or
without asthma, who were symptomatic despite standard of care
therapy, including current use of INCS for at least four weeks
prior to enrolment and a history of systemic corticosteroid use
and/or surgery for nasal polyps.1 Patients
were randomised to receive either Fasenra 30mg or placebo subcutaneously every four
weeks for the first three doses and every eight weeks
thereafter.1
The primary outcome measures of the trial were: the effect
of Fasenra on nasal polyp burden, assessed by change
from baseline in endoscopic total nasal polyp score, at week 40
compared to placebo; the effect of Fasenra on patient-reported nasal blockage, assessed
by change from baseline in mean nasal blockage score (NBS), at week
40 compared to placebo.1 OSTRO
involved 413 patients in Europe and North
America.1
OSTRO is part of AstraZeneca's clinical trial programme
for Fasenra in CRSwNP which also includes the ongoing
Phase III ORCHID trial, among others.2
ORCHID
ORCHID is a randomised, double-blinded, multi-centre,
parallel-group, 56-week Phase III trial to evaluate the efficacy
and safety of Fasenra compared to placebo in patients with
eosinophilic CRSwNP.2 The
primary outcome measures of the trial are: the effect
of Fasenra on nasal polyp burden, assessed by change
from baseline in endoscopic total nasal polyp score, at week 56
compared to placebo; the effect of Fasenra on patient-reported nasal blockage, assessed
by change from baseline in mean NBS, at week 56 compared to
placebo.2 The
trial is expected to read out in the second half of
2023.
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).13,14 Nasal
polyps are a strong indicator of the eosinophilic phenotype in
severe asthma and response to Fasenra, including reductions in exacerbation and
improvement in lung function.15-17
Fasenra is currently
approved as an add-on maintenance treatment for severe eosinophilic
asthma in the US, EU, Japan and other countries, and is approved
for self-administration in the US, EU and other
countries.
Fasenra is in development
for other eosinophilic diseases including atopic dermatitis,
bullous pemphigoid, chronic obstructive pulmonary disease, chronic
spontaneous urticaria, EoE, EG/EGE, EGPA, HES and non-cystic
fibrosis bronchiectasis.18-26
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 & 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. Bachert
C, et
al. Efficacy
and safety of benralizumab in chronic rhinosinusitis with nasal
polyps: A randomized, placebo-controlled
trial. J Allergy
Clin Immunol.
2021; [IN PRESS]. DOI: https://doi.org/10.1016/j.jaci.2021.08.030.
2.
Clinicaltrials.gov. Efficacy and Safety Study of Benralizumab in
Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps
(ORCHID). Available at: https://clinicaltrials.gov/ct2/show/NCT04157335.
[Last accessed: February 2022].
3. Bachert C, et al. Phenotypes and Emerging Endotypes of Chronic
Rhinosinusitis. J Allergy Clin Immunol
Pract. 2016; 4 (4):
621-628.
4. Newton JR, et al. A review of nasal
polyposis. Ther Clin Risk
Manag. 2008; 4 (2):
507-512.
5. Hopkins C. Chronic Rhinosinusitis
with Nasal Polyps. N Engl J
Med. 2019; 381 (1):
55-63.
6. Stevens
WW, et
al. Chronic Rhinosinusitis with
Nasal Polyps. J Allergy Clin Immunol
Pract. 2016; 4 (4):
565-572.
7. 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.
8. Ren L, et al. Biologics for the treatment of chronic
rhinosinusitis with nasal polyps - state of the
art. World Allergy Organ
J.
2019;12(8):100050.
9. DeConde
AS, et
al. Prevalence of polyp
recurrence after endoscopic sinus surgery for chronic
rhinosinusitis with nasal polyposis. The
Laryngoscope. 2017; 127 (3):
550-555.
10.
Xolair (omalizumab) US prescribing information; 2021.
11.
Dupixent (dupilumab) US prescribing information; 2021.
12.
Nucala (mepolizumab) US prescribing information; 2022.
13. Kolbeck R, et al. MEDI-563, a humanized anti-IL-5 receptor a mAb
with enhanced antibody-dependent cell-mediated cytotoxicity
function. J Allergy Clin
Immunol. 2010; 125:
1344-1353.
14. Pham T, et al. Reductions in eosinophil biomarkers by
benralizumab in patients with asthma. Respir Med. 2016; 111: 21-29.
15. Bleecker ER, et al. Efficacy and safety of benralizumab for patients
with severe asthma uncontrolled with high-dosage inhaled
corticosteroids and long-acting b2-agonists (SIROCCO): a
randomised, multicentre, placebo-controlled phase 3
trial. Lancet. 2016;388:2115-2127.
16. 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.
17. Canonica S, et al. Benralizumab improves symptoms of patients with
severe, eosinophilic asthma with a diagnosis of nasal
polyposis. Allergy. 2022;77:150-161.
18. Clinicaltrials.gov.
Efficacy and Safety Study of the Use of Benralizumab for Patients
With Moderate to Severe Atopic Dermatitis. Available
at: https://www.clinicaltrials.gov/ct2/show/NCT04605094.
[Last accessed: February 2022].
19. ClinicalTrials.gov. A
Study to Investigate the Use of Benralizumab in Patients With
Bullous Pemphigoid. (FJORD). Available at: https://clinicaltrials.gov/ct2/show/NCT04612790.
[Last accessed: February 2022].
20. Clinicaltrials.gov.
Efficacy and Safety of Benralizumab in Moderate to Very Severe
Chronic Obstructive Pulmonary Disease (COPD) With a History of
Frequent Exacerbations (RESOLUTE). Available
at: https://clinicaltrials.gov/ct2/show/NCT04053634.
[Last accessed: February 2022].
21. Clinicaltrials.gov. A
Study to Investigate the Use of Benralizumab in Patients With
Moderate to Severe Chronic Spontaneous Urticaria. (ARROYO).
Available at: https://www.clinicaltrials.gov/ct2/show/NCT04612725.
[Last accessed: February 2022].
22. Clinicaltrials.gov. A
Study of Benralizumab in Patients With Eosinophilic Esophagitis
(MESSINA). Available at: https://clinicaltrials.gov/ct2/show/NCT04543409.
[Last accessed: February 2022].
23.
AstraZeneca Data on File (HUDSON trial).
24. Clinicaltrials.gov. A
Study to Evaluate if Benralizumab Compared to Mepolizumab May be
Beneficial in the Treatment of Eosinophilic Granulomatosis With
Polyangiitis (EGPA) (MANDARA). Available
at: https://clinicaltrials.gov/ct2/show/NCT04157348.
[Last accessed: February 2022].
25. Clinicaltrials.gov. A
Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab
in Patients With Hypereosinophilic Syndrome (HES) (NATRON).
Available at: https://clinicaltrials.gov/ct2/show/NCT04191304.
[Last accessed: February 2022].
26. EU Clinical Trials
Register. A Multicentre, Randomised, Double-blind, Parallel-group,
Placebo-controlled, 52-Week, Phase III Study With an Open-label
Extension to Evaluate the Efficacy and Safety of Benralizumab in
Patients With Non-Cystic Fibrosis Bronchiectasis (MAHALE). EudraCT
number: 2020-004068-24. Available at: https://www.clinicaltrialsregister.eu/ctr-search/search?query=MAHALE.
[Last accessed: February 2022].
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:
14 March 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|