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 September 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.
Fasenra EGPA US FDA approval
18 September 2024
Fasenra approved in the US for eosinophilic
granulomatosis with polyangiitis
New indication supported by the MANDARA trial which showed nearly
60% of patients achieved remission and 41% of patients fully
stopped taking oral corticosteroids
AstraZeneca's Fasenra (benralizumab) has been approved in the US
for the treatment of adult patients with eosinophilic
granulomatosis with polyangiitis (EGPA).1 EGPA
is a rare, immune-mediated vasculitis that can result in damage to
multiple organs, and without treatment, can be
fatal.2,3
The approval by the US Food and Drug Administration
(FDA) was based on positive results from the MANDARA Phase III
trial published in The
New England Journal of Medicine,4 which
compared the efficacy and safety of Fasenra to the only approved EGPA treatment,
mepolizumab, in patients with relapsing or refractory
EGPA.4-6 MANDARA
was the first head-to-head non-inferiority trial of biologics in
patients with EGPA.5,7 Patients
were randomised to receive either a single 30 mg subcutaneous
injection of Fasenra, or three separate 100 mg subcutaneous injections
of mepolizumab every four weeks.4,5
In the trial, nearly 60% of Fasenra-treated patients achieved remission which was
comparable to mepolizumab-treated patients.4 Data
also showed 41% of Fasenra-treated patients fully tapered off oral
corticosteroids (OCS) (vs. 26% in the mepolizumab arm (difference:
16%; 95% CI: 1,31)).4
Dr. Michael Wechsler, Professor of Medicine and Director of The
Asthma Institute at National Jewish Health, and International
Coordinating Investigator of the MANDARA trial said: "This approval
is great news for patients with EGPA in the US who continue to
suffer from debilitating symptoms. Patients often rely on long-term
oral corticosteroids, which can cause serious and lasting side
effects. Benralizumab is a much-needed treatment option, with data
showing that not only is remission an achievable goal for EGPA
patients, but benralizumab can also help patients taper off steroid
therapy."
Joyce Kullman, Executive Director, Vasculitis Foundation said:
"This disease has a devastating impact on patients and the quality
of their life, and they need more treatment options. The approval
of another treatment in EGPA is welcome news to the approximately
15,000 patients living in the US with this difficult-to-treat rare
disease."
Ruud Dobber, Executive Vice President, BioPharmaceuticals Business
Unit, AstraZeneca said: "Fasenra is already well established for the
treatment of severe eosinophilic asthma, and with this approval,
physicians in the US will now be able to offer an important new,
convenient single monthly subcutaneous injection to their patients
with EGPA. Today's news demonstrates the potential
of Fasenra to help patients suffering from eosinophilic
diseases beyond severe asthma."
The safety and tolerability profile for Fasenra in the MANDARA trial was consistent with the
known profile of the medicine.4
Approximately half of patients with EGPA have adult-onset severe
eosinophilic asthma (SEA) and often have sinus and nasal
symptoms.3,8,9 Fasenra is
only the second biologic approved to treat this
disease.4,5
Fasenra is currently
approved as an add-on maintenance treatment for SEA in more than 80
countries including the US, Japan, EU and China.10-13 It
is also approved in children and adolescents ages six and above in
the US and Japan. The FDA granted Orphan Drug Designation
for Fasenra for EGPA in 2018.14
Notes
Eosinophilic granulomatosis with polyangiitis
EGPA, formerly known as Churg-Strauss Syndrome, is a rare,
immune-mediated inflammatory disease that is caused by inflammation
of small to medium-sized blood vessels.2,3 It
is estimated that 118,000 people throughout the world live with
EGPA and approximately 15,000 patients
living in the US have EGPA.15,16 EGPA
can result in damage to multiple organs, including lungs, upper
airway, skin, heart, gastrointestinal tract and
nerves.3 The
most common symptoms and signs include extreme fatigue, weight
loss, muscle and joint pain, rashes, nerve pain, sinus and nasal
symptoms, and shortness of breath.3,17 Without
treatment, the disease may be fatal.3,17 Almost
half (47%) of patients do not achieve remission with current
treatments.18
There are limited treatment options for EGPA. Patients are often
treated with chronic high-dose OCS and experience recurrent
relapses when attempting to taper off OCS.17,19
MANDARA
MANDARA was a Phase III, randomised, double-blinded,
active-controlled trial, which compared the efficacy and safety
of Fasenra to mepolizumab in adult patients with
relapsing or refractory EGPA.5 In
the trial, 140 patients were randomised 1:1 to receive either a
single 30mg subcutaneous injection of Fasenra or three separate 100mg subcutaneous
injections of the active comparator every four
weeks.4
The primary endpoint was the proportion of patients who were in
remission at both weeks 36 and 48.5 Remission
is defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS
dose less than or equal to 4 mg/day.5 A
secondary endpoint was the proportion of patients who were able to
fully taper off OCS at weeks 48 through 52.5 The
primary statistical analysis was to demonstrate non-inferiority
of Fasenra versus mepolizumab based on the primary
endpoint.4
Fasenra
Fasenra (benralizumab) is
currently approved in more than 80 countries, including the US, EU,
Japan and China.10-13 Fasenra has
been prescribed to over 130,000 patients
globally.20
Fasenra is in development
for other diseases including chronic obstructive pulmonary
disease, chronic rhinosinusitis with nasal polyps and
hypereosinophilic syndrome.21-23
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 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.
Fasenra (benralizumab) US prescribing information;
September 2024.
2.
Furuta S, et al. Update on eosinophilic granulomatosis with
polyangiitis. Allergol
Int.
2019;68:430-436.
3.
American
Partnership for Eosinophilic Disorders. Eosinophilic Granulomatosis
with Polyangiitis (EGPA). Available at:
https://apfed.org/about-ead/eosinophilic-granulomatosis-with-polyangiitis/.
[Last accessed: September 2024].
4.
Wechsler ME, et al. Benralizumab versus Mepolizumab for Eosinophilic
Granulomatosis with Polyangiitis. N Engl J
Med. 2024;390(10):911-921.
5.
Clinicaltrials.gov. Efficacy and
Safety of Benralizumab in EGPA Compared to Mepolizumab. (MANDARA).
Available at: https://classic.clinicaltrials.gov/ct2/show/NCT04157348.
[Last accessed: September 2024].
6.
Mepolizumab
US prescribing information. Available from:
https://www.fda.gov/files/drugs/published/125526-Mepolizumab-Clinical-PREA.pdf [Last
accessed: September 2024].
7.
AstraZeneca plc. MANDARA Phase
III data published in New England Journal of Medicine show
remission is an achievable goal in eosinophilic granulomatosis with
polyangiitis (EGPA) with Fasenra. Available at: https://www.astrazeneca.com/media-centre/medical-releases/mandara-phase-iii-data-published-new-england-journal-medicine-show-remission-achievable-goal-eosinophilic-granulomatosis-polyangiitis-egpa-fasenra.html.
[Last accessed: September 2024].
8.
Cottin V, et al. Respiratory manifestations of eosinophilic
granulomatosis with polyangiitis
(Churg-Strauss). Eur Respir
J.
2016;48:1429-1441.
9.
Heaney L et al. Eosinophilic and Noneosinophilic Asthma: An
Expert Consensus Framework to Characterize Phenotypes in a Global
Real-Life Severe Asthma Cohort. Chest. 2021 Sep;160(3):814-830.
10.
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: September 2024].
11.
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: September 2024].
12.
AstraZeneca Annual Report 2023.
Available at: https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-report-2023/pdf/AstraZeneca_AR_2023.pdf.
[Last accessed: September 2024].
13.
AstraZeneca news release. Fasenra
met the primary endpoint in the MANDARA Phase III trial in
eosinophilic granulomatosis with polyangiitis (EGPA). Available
at: https://www.astrazeneca.com/media-centre/press-releases/2023/fasenra-phase-iii-egpa-trial-met-primary-endpoint.html#:~:text=Positive%20high%2Dlevel%20results%20from,EGPA)%20who%20were%20receiving%20oral.
[Last accessed: September 2024].
14.
AstraZeneca news release.
Available at: https://www.astrazeneca.com/media-centre/press-releases/2018/us-fda-grants-fasenra-orphan-drug-designation-for-eosinophilic-granulomatosis-with-polyangiitis-26112018.html.
[Last
accessed: September 2024].
15.
IQVIA
data on file. 2024.
16.
AstraZeneca Data on file. 2024.
REF- 244520.
17.
Baldini C, et al. Clinical Manifestations and
Treatment of Churg-Strauss Syndrome. Rheum Dis Clin N
Am.
2010;36:527-543.
18.
Wechsler ME, et al. Mepolizumab or Placebo for Eosinophilic
Granulomatosis with Polyangiitis. N Engl J
Med. 2017:376;1921-1932.
19.
Bell CF, et al. Burden of illness and costs associated with
eosinophilic granulomatosis with polyangiitis: evidence from a
managed care database in the United
States. J
Manag Care Spec Pharm.
2021;27(9):1249-1259.
20.
AstraZeneca
data on file. 2024. REF-235794.
21.
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 from: https://clinicaltrials.gov/ct2/show/NCT04053634 [Last
accessed: September 2024].
22.
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: September 2024].
23.
Clinicaltrials.gov. A Phase 3
Study to Evaluate the Efficacy and Safety of Benralizumab in
Patients With Hypereosinophilic Syndrome (HES) (NATRON). Available
from: https://clinicaltrials.gov/ct2/show/NCT04191304 [Last
accessed: September 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:
18 September 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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