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 December 2022
Commission File
Number: 001-11960
AstraZeneca
PLC
1
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Cambridge
Biomedical Campus
Cambridge CB2
0AA
United
Kingdom
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AstraZeneca
PLC
INDEX
TO EXHIBITS
1.
Enhertu recommended for EU approval in HER2-low BC
19
December 2022 07:20 GMT
Enhertu recommended
for approval in the EU by CHMP for patients
with HER2-low metastatic breast cancer
AstraZeneca and Daiichi Sankyo's Enhertu is the first HER2-directed
therapy to demonstrate a significant survival benefit vs.
chemotherapy in this patient population
AstraZeneca and Daiichi
Sankyo's Enhertu (trastuzumab deruxtecan) has been
recommended for approval in the European Union (EU) as monotherapy
for the treatment of adult patients with unresectable or
metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have
received prior chemotherapy in the metastatic setting or developed
disease recurrence during or within six months of completing
adjuvant chemotherapy.
Enhertu is a specifically engineered HER2-directed
antibody drug conjugate (ADC) being jointly developed and
commercialised by AstraZeneca and Daiichi
Sankyo.
The Committee for Medicinal Products for Human Use
(CHMP) of the European Medicines Agency based its positive opinion
on results from the DESTINY-Breast04 Phase
III trial, which were presented at the American Society
of Clinical Oncology 2022 Annual Meeting and simultaneously
published in The
New England Journal of Medicine.1
In the trial, Enhertu reduced the risk of disease progression or
death by 50% versus physician's choice of chemotherapy (based on a
hazard ratio [HR] of 0.50; 95% confidence interval [CI]: 0.40-0.63;
p<0.001) in patients with HER2-low metastatic breast cancer with
HR-positive or HR-negative disease. A median progression-free
survival (PFS) of 9.9 months was seen with Enhertu versus 5.1 months in those treated with
chemotherapy, as assessed by blinded independent central review
(BICR). A 36% reduction in the risk of death (HR 0.64; 95% CI:
0.49-0.84; p=0.001) was seen with Enhertu compared to chemotherapy with a median
overall survival (OS) of 23.4 months versus 16.8
months.
Susan Galbraith, Executive Vice President,
Oncology R&D, AstraZeneca, said: "Enhertu is the first-ever HER2-directed medicine to
show a survival benefit in patients with HER2-low metastatic breast
cancer, confirming the importance of targeting lower levels of HER2
expression in patients previously classified as HER2-negative. The
CHMP's recommendation is encouraging and supports our ambition to
evolve the way breast cancer is classified and treated to
ultimately improve patient outcomes."
Ken
Takeshita, Global Head,
R&D Daiichi Sankyo, said: "This positive
CHMP opinion recognises the unmet need in the European Union for
patients with HER2-low metastatic breast cancer. Currently, once patients with HR-positive
disease progress on hormone therapy there are limited effective
treatments, and few targeted options are available for patients
with HR-negative disease. We look forward to the
European Commission decision and aim to
bring Enhertu to
eligible patients as soon as possible."
The safety profile observed in patients treated
with Enhertu in the DESTINY-Breast04 trial was consistent
with that seen in other trials of Enhertu in breast cancer with no new safety signals
identified.
Notes
Breast cancer and HER2 expression
Breast cancer is the most common cancer and is one
of the leading causes of cancer-related deaths
worldwide.2 More
than two million patients with breast cancer were diagnosed in 2020
with nearly 685,000 deaths globally.2 In
Europe, approximately 531,000 breast cancer patients are diagnosed
annually with nearly 141,000 deaths.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, and
is one of many biomarkers expressed in breast cancer
tumours.4
HER2 expression is currently determined by an
immunohistochemistry (IHC) test which estimates the amount of HER2
protein on a cancer cell, and/or an in situ hybridisation (ISH)
test, which counts the copies of the HER2 gene in cancer
cells.4,5 HER2
tests provide IHC and ISH scores across the full HER2 spectrum and
are routinely used to determine appropriate treatment options for
patients with metastatic breast cancer.
HER2-positive cancers are currently defined as
HER2 expression measured as IHC 3+ or IHC 2+/ISH+, and
HER2-negative cancers are defined as HER2 expression measured as
IHC 0, IHC 1+ or IHC 2+/ISH-.4 However,
approximately half of all breast cancers are HER2-low, defined as a
HER2 score of IHC1+ or IHC 2+/ISH-.6-8 HER2-low
occurs in both HR-positive and HR-negative
disease.9
Currently, patients with HR-positive metastatic
breast cancer and HER2-low disease have limited effective treatment
options following progression on endocrine (hormone)
therapy.10 Additionally,
few targeted options are available for those with HR-negative
disease.11
DESTINY-Breast04
DESTINY-Breast04 is a global, randomised,
open-label, Phase III trial evaluating the efficacy and safety
of Enhertu (5.4mg/kg) versus physician's choice of
chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel or
nab-paclitaxel) in patients with HR-positive or HR-negative,
HER2-low unresectable and/or metastatic breast cancer previously
treated with one or two prior lines of chemotherapy. Patients were
randomised 2:1 to receive either Enhertu or chemotherapy.
The
primary endpoint of DESTINY-Breast04 is PFS in patients with
HR-positive disease based on BICR. Key secondary endpoints include
PFS based on BICR in all randomised patients (HR-positive and
HR-negative disease), OS in patients with HR-positive disease and
OS in all randomised patients (HR-positive and HR-negative
disease). Other secondary endpoints include PFS based on
investigator assessment, objective response rate based on BICR and
on investigator assessment, duration of response based on BICR and
safety.
DESTINY-Breast04 enrolled 557 patients at multiple
sites in Asia, Europe and North 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 40
countries for the treatment of adult patients with unresectable or
metastatic HER2-positive breast cancer who have received a (or one
or more) prior anti-HER2-based regimen, either in the metastatic
setting or in the neoadjuvant or adjuvant setting and have
developed disease recurrence during or within six months of
completing therapy, based on the results from the DESTINY-Breast03
trial. Enhertu also is approved in several 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.
Enhertu (5.4mg/kg) is approved in Brazil and the US
for the treatment of adult patients with unresectable or metastatic
HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a
prior systemic therapy in the metastatic setting or developed
disease recurrence during or within six months of completing
adjuvant chemotherapy, based on the results of the DESTINY-Breast04
trial.
Enhertu (5.4mg/kg) is approved under accelerated
approval in the US for the treatment of adult patients with
unresectable or metastatic non-small cell lung cancer whose tumours
have activating HER2 (ERBB2) mutations, as detected by an
FDA-approved test, and who have received a prior systemic therapy
based on the results from the DESTINY-Lung02 trial. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in a confirmatory
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 and/or the
DESTINY-Gastric02 trial.
Enhertu development
programme
A comprehensive global development programme is
underway 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.
Regulatory applications
for Enhertu in breast, non-small cell lung and gastric
cancer are currently under review in several
countries.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568)
[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 the 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.
With Enhertu (trastuzumab deruxtecan), a HER2-directed
ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes
in previously treated HER2-positive and HER2-low metastatic breast
cancer and are exploring its potential in earlier lines of
treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca
continues to improve outcomes with foundational
medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the
HR-positive space with ngSERD and potential new medicine
camizestrant as well as a potential first-in-class AKT kinase
inhibitor, capivasertib. AstraZeneca is also collaborating with
Daiichi Sankyo to explore the potential of TROP2-directed ADC,
datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option
that has been studied in early and metastatic breast cancer with an
inherited BRCA mutation. AstraZeneca with MSD (Merck & Co.,
Inc. in the US and Canada) continue to
research Lynparza in these settings and to explore its
potential in earlier disease.
To bring much-needed treatment options to patients
with triple-negative breast cancer, an aggressive form of breast
cancer, AstraZeneca is evaluating the potential of datopotamab
deruxtecan alone and in combination with
immunotherapy Imfinzi (durvalumab), capivasertib in combination
with chemotherapy, and Imfinzi in combination with other oncology
medicines, including Lynparza and Enhertu.
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. Modi S, et al. Trastuzumab
Deruxtecan in Previously Treated HER2-Low Advanced Breast
Cancer. N Engl J
Med 2022;
387:9-20.
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. WHO. International Agency of Cancer
Research. Cancer Today. Breast Cancer. 2020. Available
at: https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf.
Accessed December 2022.
4. Iqbal N, et al. Human Epidermal
Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and
Therapeutic Implications. Mol Biol
Int. 2014;
852748.
5. Wolff A, et al. Human Epidermal
Growth Factor Receptor 2 Testing in Breast Cancer: American Society
of Clinical Oncology/College of American Pathologists Clinical
Practice Guideline Focused Update. Arch Pathol Lab
Med. 2018; 142(11):
1364-1382.
6. Schettini F, et al. Clinical,
pathological, and PAM50 gene expression features of HER2-low breast
cancer. NPJ Breast
Cancer. 2021; 7:1;
https://doi.org/10.1038/s41523-020-00208-2.
7. Schalper K, et al. A retrospective
population-based comparison of HER2 immunohistochemistry and
fluorescence in situ hybridization in breast
carcinomas. Arch Pathol Lab
Med. 2014; 138:
213-219.
8. Denkert C, et al. Clinical and
molecular characteristics of HER2-low-positive breast cancer:
pooled analysis of individual patient data from four prospective,
neoadjuvant clinical trials. 2021. Lancet
Oncol; 22:
1151-61.
9. Miglietta F, et al. Evolution of
HER2-low expression from primary to recurrent breast
cancer. NPJ Breast
Cancer. 2021; 7:137;
10.1038/s41523-021-00343-4.
10. Matutino A, et al. Hormone
receptor-positive, HER2-negative metastatic breast cancer:
redrawing the lines. Current
Oncology. 2018; 25(S1):
S131-S141.
11. American Cancer Society. Breast Cancer
Hormone Receptor Status. Available at: https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-hormone-receptor-status.html.
Accessed December 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:
19 December 2022
|
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By: /s/
Adrian Kemp
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|
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Name:
Adrian Kemp
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Title:
Company Secretary
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