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 approved in the EU for patients with
previously treated HER2-positive advanced gastric
cancer
19
December 2022 07:15 GMT
Enhertu approved
in the EU for patients with previously treated HER2-positive
advanced gastric cancer
First HER2-directed medicine to be approved for gastric cancer in
the EU in more than a decade
Based on DESTINY-Gastric02 and DESTINY-Gastric01 where AstraZeneca
and Daiichi Sankyo's Enhertu demonstrated clinically meaningful
efficacy
AstraZeneca and Daiichi
Sankyo's Enhertu (trastuzumab deruxtecan) has been approved
in the European Union (EU) as monotherapy for the treatment of
adult patients with advanced HER2-positive gastric or
gastroesophageal junction (GEJ) adenocarcinoma who have received a
prior trastuzumab-based regimen.
Enhertu is a specifically engineered HER2-directed
antibody drug conjugate (ADC) being jointly developed and
commercialised by AstraZeneca and Daiichi
Sankyo.
The approval by the European Commission follows
the positive
opinion of the Committee
for Medicinal Products for Human Use in November 2022 and is based
on results from the DESTINY-Gastric02 and DESTINY-Gastric01
Phase II trials.
In DESTINY-Gastric02, which enrolled patients
from North America and Europe, treatment
with Enhertu resulted in a confirmed objective response
rate (ORR) of 41.8% as assessed by independent central review
(ICR). Median duration of response (DoR) was 8.1
months.
In DESTINY-Gastric01, which enrolled patients from
Japan and South Korea, treatment with Enhertu resulted in a confirmed ORR of 40.5%
versus 11.3% with chemotherapy (irinotecan or paclitaxel) as
assessed by ICR. The median DoR was 11.3 months
with Enhertu versus 3.9 months with chemotherapy.
Patients treated with Enhertu had a 41% reduction in the risk of death
versus patients treated with chemotherapy (based on a hazard ratio
of 0.59; 95% confidence interval: 0.39-0.88; p=0.0097) with a
median overall survival (OS) of 12.5 months versus 8.4
months.
Approximately 136,000
cases of gastric cancer are diagnosed annually in Europe, where it
represents the sixth leading cause of cancer
death.1,2 Gastric
cancer is typically diagnosed in the advanced stage. Even when the
disease is diagnosed at earlier stages, the survival rate remains
modest.3,4 Approximately
one in five gastric cancers are HER2-positive.5,6
Eric Van Cutsem, MD,
PhD, Head of Department of
Oncology at the University of Leuven, Belgium and Founding Chair of
the ESMO-GI/World Congress of Gastrointestinal
Cancers, said: "Today's news is a welcome
advance for patients with
HER2-positive advanced gastric cancer. Patients with this
disease face poor outcomes following progression on initial
treatment with a HER2-directed medicine as many do not respond to further treatment,
and even those that do respond often do not have durable
responses. Data from the DESTINY-Gastric02
and DESTINY-Gastric01 trials support Enhertu becoming
a new standard of care for patients in this setting."
Dave Fredrickson, Executive Vice President,
Oncology Business Unit, AstraZeneca, said: "Today's important
approval makes Enhertu the
first HER2-directed medicine to be approved for gastric cancer in
the European Union in more than a decade. Patients across the EU
with advanced HER2-positive disease who have progressed following
treatment in the first-line setting, may now have the opportunity
to benefit from treatment with Enhertu."
Ken Keller, Global Head of Oncology Business, and
President and CEO, Daiichi Sankyo, Inc., said: "Enhertu is
the first antibody drug conjugate to be approved in Europe for
advanced gastric cancer, representing a major advance in
treating this difficult-to-treat cancer. With this approval, we can now
offer patients with previously treated HER2-positive gastric cancer
a treatment with clinically meaningful
efficacy."
In both trials, the safety profiles observed in
patients treated with Enhertu were consistent with those seen in other
trials of Enhertu with no new safety signals
identified.
Enhertu is also approved in the US and several other
countries for locally advanced or metastatic HER2-positive gastric
cancer.
Notes
Financial considerations
Following
EU approval, an amount of $35m is due from AstraZeneca to Daiichi
Sankyo as a milestone payment for the previously treated
HER2-positive gastric indication. The milestone payment will be
capitalised as an addition to the upfront payment made by
AstraZeneca to Daiichi Sankyo in 2019 and subsequent capitalised
milestones.
Sales of Enhertu in most EU territories are recognised by
Daiichi Sankyo. AstraZeneca reports its share of gross profit
margin from Enhertu sales in those territories as collaboration
revenue in the Company's financial statements. AstraZeneca will
record product sales in respect of sales made in territories where
AstraZeneca is the selling party.
Further details on the financial arrangements were
set out in the March 2019
announcement of the
collaboration.
HER2-positive gastric cancer
Gastric (stomach) cancer is the fifth most common
cancer worldwide and the fourth highest leading cause of cancer
mortality, with a five-year global survival rate of 5% to 10% for
advanced or metastatic disease.3,7,8 Approximately
one million new patients were diagnosed with gastric cancer in
2020, with 768,000 deaths reported globally.2 In
Europe, approximately 136,000 cases of gastric cancer are diagnosed
annually, and Eastern Europe has the second highest incidence of
gastric cancer worldwide after Eastern Asia.2,8 Gastric
cancer is the sixth leading cause of cancer death in Europe and is
typically diagnosed in the advanced stage. Even when diagnosed in
earlier stages of the disease, the survival rate remains
modest.1,3,4
Approximately one in five gastric cancers are
HER2-positive.5,6 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.5 HER2
overexpression may be associated with a specific HER2 gene
alteration known as HER2 amplification.6
Recommended first-line treatment in the EU for
HER2-positive advanced or metastatic gastric cancer is combination
chemotherapy plus trastuzumab, an anti-HER2 medicine, which has
been shown to improve survival outcomes when added to
chemotherapy.9,10 For
patients with metastatic gastric cancer that progresses following
initial treatment with a trastuzumab-based regimen, there were
previously no other approved HER2-directed medicines in the EU
prior to the approval of Enhertu.7,11,12
DESTINY-Gastric02
DESTINY-Gastric02 is an open-label, single-arm
Phase II trial in patients evaluating the efficacy and safety
of Enhertu (6.4mg/kg) in patients with HER2-positive
metastatic and/or unresectable gastric or GEJ adenocarcinoma with
disease progression on or after a trastuzumab-containing
regimen.
The
primary endpoint of DESTINY-Gastric02 is confirmed ORR based on
ICR. Secondary endpoints include progression-free survival (PFS),
OS, DoR and safety.
DESTINY-Gastric02 enrolled 79 patients at multiple
sites in North America and Europe. For more information about
the trial, visit ClinicalTrials.gov.
DESTINY-Gastric01
DESTINY-Gastric01 is a randomised, open-label
Phase II trial evaluating the efficacy and safety
of Enhertu (6.4mg/kg) in patients with primarily
HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC
2+/in-situ hybridisation [ISH]+) advanced gastric cancer or GEJ
adenocarcinoma with disease progression following two or more prior
treatment regimens including fluoropyrimidine (5-FU), platinum
chemotherapy and trastuzumab. Patients were randomised 2:1 to
receive Enhertu or physician's choice of chemotherapy
(paclitaxel or irinotecan monotherapy).
The
primary endpoint of DESTINY-Gastric01 is ORR. Secondary endpoints
include OS, PFS, DoR, disease control rate and time to treatment
failure, as well as pharmacokinetic and safety
endpoints.
DESTINY-Gastric01 enrolled 187 patients at
multiple sites in Japan and South Korea. 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 (5.4mg/kg) 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 chemotherapy in the metastatic setting or developed disease
recurrence during or within six months of completing adjuvant
chemotherapy based on the results from 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 of 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 GEJ who have received a prior
trastuzumab-based regimen based on the results from the
DESTINY-Gastric01 and/or DESTINY-Gastric02
trial.
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.
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 gastrointestinal cancers
AstraZeneca has a broad development programme for
the treatment of gastrointestinal (GI) cancers across several
medicines and a variety of tumour types and stages of disease. In
2020, GI cancers collectively represented approximately 5.1 million
new cancer cases leading to approximately 3.6 million
deaths.13
Within
this programme, the Company is committed to improving outcomes in
gastric, liver, biliary tract, oesophageal, pancreatic and
colorectal cancers.
Imfinzi (durvalumab) is approved in the US in
combination with chemotherapy (gemcitabine plus cisplatin) for
advanced biliary tract cancer and in combination
with Imjudo in
unresectable hepatocellular
carcinoma. Imfinzi is being assessed
in combinations, including with Imjudo in
liver, oesophageal and gastric cancers in an extensive development
programme spanning early to late-stage disease across
settings.
Enhertu, a HER2-directed antibody drug conjugate, is
approved in HER2-positive advanced gastric cancer and is being
assessed in colorectal cancer. Enhertu is jointly developed and commercialised by
AstraZeneca and Daiichi Sankyo.
Lynparza (olaparib), a first-in-class PARP inhibitor,
is approved in BRCA-mutated metastatic pancreatic
cancer. Lynparza is developed and commercialised in
collaboration with MSD (Merck & Co., Inc. inside the US and
Canada).
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. WHO.
Cancer Today Europe Mortality. Available at: https://gco.iarc.fr/today/online-analysis-table. Accessed
December 2022.
2. WHO. International
Agency of Cancer Research. Cancer Today. Stomach Incidence. 2020.
Available at: https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf.
Accessed December 2022.
3. SEER
Cancer Stat Facts: Stomach Cancer. Available at: https://seer.cancer.gov/statfacts/html/stomach.html.
Accessed December 2022.
4. Cancer
Research UK. Stomach Cancer Survival
Statistics. Available
at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/stomach-cancer/survival#heading-Zero. Accessed
December 2022.
5. Iqbal
N, et al. Human epidermal growth factor receptor 2 (HER2) in
cancers: overexpression and therapeutic
implications. Mol Biol
Int. 2014;
2014:852748.
6. Abrahao-Machado
LF, et al. HER2 testing in gastric cancer: an
update. World J
Gastroenterol. 2016;
22(19):4619-4625.
7. Casamayor
M, et al. Targeted literature review of the global burden of
gastric cancer. Ecancermedicalscience.
2018; 12:883.
8. 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; 71(3):209-249.
9. Orditura
M, et al. Treatment of gastric cancer. World
J Gastroenterol. 2014;
20(7):1635-1649.
10. Lordick
F, et al. Gastric cancer: ESMO Clinical Practice Guideline for
diagnosis, treatment and follow-up. Ann
Oncol. 2022
Oct;33(10):1005-1020.
11. Thuss-Patience
PC, et al. Trastuzumab emtansine versus taxane use for
previously treated HER2-positive locally advanced or metastatic
gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an
international randomised, open-label, adaptive, phase 2/3
study. Lancet
Oncol. 2017;
18(5):640-653.
12. Satoh
T, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the
second-line treatment of HER2-amplified advanced gastric cancer in
asian populations: TyTAN-a randomized, phase III
study. J Clin
Oncol. 2014;
32(19):2039‐2049.
13. WHO.
World Cancer Fact Sheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
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
|
|
By: /s/
Adrian Kemp
|
|
|
Name:
Adrian Kemp
|
|
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Title:
Company Secretary
|
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