a6391y
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 January 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.
Enhertu
granted Priority Review for breast cancer
17 January 2022 07:00 GMT
Enhertu granted Priority Review in the US for
patients with HER2-positive metastatic breast cancer treated with a
prior anti-HER2-based regimen
Based on ground-breaking DESTINY-Breast03 results showing
AstraZeneca and Daiichi Sankyo's Enhertu reduced the risk of
disease progression or death by 72% versus trastuzumab emtansine
(T-DM1)
Application being evaluated under FDA Real-Time Oncology Review and
Project Orbis
AstraZeneca and Daiichi Sankyo have received notification of
acceptance of the supplemental Biologics License Application (sBLA)
of Enhertu (trastuzumab deruxtecan) for the treatment
of adult patients in the US with unresectable or metastatic
HER2-positive breast cancer who have received a prior
anti-HER2-based regimen. The application has also
been granted Priority Review.
Enhertu is a HER2-directed
antibody drug conjugate (ADC) being jointly developed by
AstraZeneca and Daiichi Sankyo.
The Food and Drug Administration (FDA) grants Priority Review to
applications for medicines that, if approved, would offer
significant improvements over available options by demonstrating
safety or efficacy improvements, preventing serious conditions, or
enhancing patient compliance.1 The
Prescription Drug User Fee Act (PDUFA) date, the FDA action date
for their regulatory decision, is during the second quarter of
2022.
The sBLA is being reviewed under the Real-Time Oncology Review
(RTOR) programme and Project Orbis, two initiatives of the FDA
which are designed to bring effective cancer treatments to patients
as early as possible. RTOR allows the FDA to review components of
an application before submission of the complete application.
Project Orbis provides a framework for concurrent submission and
review of oncology medicines among participating international
partners.
Breast cancer is the most common cancer worldwide, with more than
two million cases diagnosed in 2020, resulting in nearly 685,000
deaths globally.2 Approximately
one in five cases of breast cancer are considered
HER2-positive.3 Despite
initial treatment with trastuzumab and a taxane, patients with
HER2-positive metastatic breast cancer will often experience
disease progression.4 More
treatment options are needed to further delay progression and
extend survival.4-6
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca said: "This review across geographies and the Priority
Review in the US as part of Project Orbis is so important because
it speaks to the transformative potential
of Enhertu based on the unprecedented progression-free
survival benefit in this setting. The news reinforces the
importance of bringing this potential new option to patients as
quickly as possible."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "This
regulatory review of Enhertu in the US marks the first time this medicine
is participating in both the Real-Time Oncology Review and Project
Orbis programmes. The FDA's prioritisation of our application
underscores the potential of this medicine and the continued need
to expedite the availability of new treatment options, while making
it possible to potentially receive approvals in several countries
concurrently."
The sBLA is based on data from the DESTINY-Breast03
trial presented during
the European Society for Medical Oncology
(ESMO) Congress 2021.
In the trial, Enhertu demonstrated a 72% reduction in the risk of
disease progression or death compared to T-DM1 (hazard ratio [HR]
0.28; 95% confidence interval [CI]: 0.22-0.37;
p=7.8x10-22)
in patients with HER2-positive unresectable and/or metastatic
breast cancer previously treated with trastuzumab and a
taxane.
DESTINY-Breast03 also recorded that nearly all patients treated
with Enhertu during the trial were alive at one year
(94.1%) compared to 85.9% of patients treated with T-DM1. Confirmed
objective response rate (ORR) more than doubled in
the Enhertu arm versus the T-DM1 arm (79.7% vs. 34.2%).
The safety profile of Enhertu was consistent with previous clinical
trials, with no new safety concerns identified and no Grade 4 or 5
treatment-related interstitial lung disease
events.
In September 2021, Enhertu received its fourth Breakthrough Therapy
Designation (BTD) in the
US for the treatment of adult patients with unresectable or
metastatic HER2-positive breast cancer who have received one or
more prior anti-HER2-based regimens.
Enhertu is approved for
the treatment of adult patients with unresectable or metastatic
HER2-positive breast cancer who have received two or more prior
anti-HER2-based regimens in more than 30 countries based on the
results from the DESTINY-Breast01 trial.
Enhertu is being further
assessed in a comprehensive clinical development programme
evaluating efficacy and safety across multiple HER2-targetable
cancers, including breast, gastric, lung and colorectal
cancers.
Notes
HER2-positive breast cancer
Breast cancer is the most common cancer and is one of the leading
causes of cancer-related deaths in women
worldwide.2 More
than two million patients with breast cancer were diagnosed in
2020, resulting in nearly 685,000 deaths
globally.2 Approximately
one in five cases of breast cancer are considered
HER2-positive.3
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours, including
breast, gastric, lung and colorectal cancers.7 HER2
protein overexpression may occur as a result of HER2 gene
amplification and is often associated with aggressive disease and
poor prognosis in breast cancer.8
Despite initial treatment with trastuzumab and a taxane, people
with HER2-positive metastatic breast cancer will often experience
disease progression.4 More
treatment options are needed to further delay progression and
extend survival.4-6
DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label,
registrational Phase III trial evaluating the safety and efficacy
of Enhertu (5.4mg/kg) versus T-DM1 in patients with
HER2-positive unresectable and/or metastatic breast cancer
previously treated with trastuzumab and a
taxane.
The primary efficacy endpoint of DESTINY-Breast03 is
progression-free survival (PFS) based on blinded independent
central review. Secondary efficacy endpoints include overall
survival, ORR, duration of response, PFS based on investigator
assessment and safety.
DESTINY-Breast03 enrolled approximately 500 patients at
multiple sites in Asia, Europe, North America, Oceania and South
America. For more information about the trial,
visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed
ADC. Designed using Daiichi Sankyo's proprietary DXd ADC
technology, Enhertu is the lead ADC in the oncology portfolio of
Daiichi Sankyo and the most advanced programme in AstraZeneca's ADC
scientific platform. Enhertu consists of a HER2 monoclonal antibody
attached to a topoisomerase I inhibitor payload, an exatecan
derivative, via a stable tetrapeptide-based cleavable
linker.
Enhertu (5.4mg/kg) is
approved in more than 30 countries for the treatment of adult
patients with unresectable or metastatic HER2-positive breast
cancer who have received two or more prior anti-HER2-based regimens
based on the results from the DESTINY-Breast01 trial. A Type II
Variation is currently under review by the European Medicines
Agency (EMA) for the treatment of adult patients with unresectable
or metastatic HER2-positive breast cancer who have received one or
more prior anti-HER2-based regimens based on the results from the
DESTINY-Breast03 trial.
Enhertu (6.4mg/kg) is
approved in several countries for the treatment of adult patients
with locally advanced or metastatic HER2-positive gastric or
gastroesophageal junction adenocarcinoma who have received a prior
trastuzumab-based regimen based on the results from the
DESTINY-Gastric01 trial. A Type II Variation is currently under
review by the EMA for the treatment of adult patients with locally
advanced or metastatic HER2-positive gastric or gastroesophageal
junction adenocarcinoma who have received a prior anti-HER2-based
regimen.
Enhertu development
programme
A comprehensive development programme is underway globally,
evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable
cancers, including breast, gastric, lung and colorectal cancers.
Trials in combination with other anticancer treatments, such as
immunotherapy, are also underway.
Enhertu was highlighted in
the Clinical Cancer Advances 2021 report as one of two significant
advancements in the "ASCO Clinical Advance of the Year: Molecular
Profiling Driving Progress in GI Cancers," based on data from both
the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of
the targeted therapy advances of the year in non-small cell lung
cancer (NSCLC), based on the interim results of the HER2-mutated
cohort of the DESTINY-Lung01 trial.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and
AstraZeneca entered into a global collaboration to jointly develop
and commercialise Enhertu (a HER2-directed ADC) in March 2019, and
datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July
2020, except in Japan where Daiichi Sankyo maintains exclusive
rights. Daiichi Sankyo is responsible for manufacturing and supply
of Enhertu and datopotamab
deruxtecan.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology,
AstraZeneca is starting to challenge, and redefine, the current
clinical paradigm for how breast cancer is classified and treated
to deliver even more effective treatments to patients in need -
with the bold ambition to one day eliminate breast cancer as a
cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising
compounds in development that leverage different mechanisms of
action to address the biologically diverse breast cancer tumour
environment. AstraZeneca aims to continue to transform outcomes for
HR-positive breast cancer with foundational
medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation oral
selective oestrogen receptor degrader (SERD) and potential new
medicine camizestrant.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option
for metastatic breast cancer patients with an inherited BRCA
mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and
Canada) continue to research Lynparza in metastatic breast cancer patients with an
inherited BRCA mutation and are exploring new opportunities to
treat these patients earlier in their disease.
Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated
HER2-positive metastatic breast cancer, AstraZeneca and Daiichi
Sankyo are exploring its potential in earlier lines of treatment
and in new breast cancer settings.
To bring much needed treatment options to patients with
triple-negative breast cancer, an aggressive form of breast cancer,
AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other
oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase
inhibitor, capivasertib, in combination with chemotherapy, and
collaborating with Daiichi Sankyo to explore the potential of
TROP2-directed ADC, datopotamab deruxtecan.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition
to provide cures for cancer in every form, following the science to
understand cancer and all its complexities to discover, develop and
deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It
is through persistent innovation that AstraZeneca has built one of
the most diverse portfolios and pipelines in the industry, with the
potential to catalyse changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day,
eliminate cancer as a cause of death.
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. FDA. Priority Review. Available at:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
Accessed January 2022.
2. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN
Estimates of Incidence and Mortality Worldwide for 36 Cancers in
185 Countries. CA Cancer J
Clin. 2021;
10.3322/caac.21660.
3. Ahn S, et al. HER2 status in breast cancer: changes in
guidelines and complicating factors for
interpretation. J Pathol Transl
Med. 2020; 54(1):
34-44.
4. Barok M, et al. Trastuzumab emtansine: mechanism of action and
drug resistance. Breast Cancer
Res. 2014;
16(2):209.
5. Mounsey L, et al. Changing Natural History of HER2-Positive Breast
Cancer Metastatic to the Brain in the Era of New Targeted
Therapies. Clin Breast
Cancer. 2018;
18(1):29-37.
6. Martinez-S Sáez O, et al. Current and Future Management of HER2-Positive
Metastatic Breast Cancer. JCO Oncol
Pract. 2021.
10.1200/OP.21.00172.
7. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2)
in Cancers: Overexpression and Therapeutic
Implications. Mol Biol
Int.
2014;852748.
8. Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report
from the Lung Cancer Mutation Consortium. Cancer. 2017;1;123(21):4099-4105.
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:
17 January 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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