a9430s
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 July 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
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United
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu approved in EU for HER2-positive mBC
19 July 2022 07:00 BST
Enhertu approved
in the EU for patients with HER2-positive metastatic breast cancer
treated with one or more prior anti-HER2-based
regimens
Approval broadens indication for AstraZeneca and Daiichi Sankyo's
Enhertu across Europe to earlier use in HER2-positive metastatic
breast cancer
Based on ground-breaking DESTINY-Breast03 results in which Enhertu
demonstrated a 72% reduction in the risk of disease progression or
death vs. trastuzumab emtansine (T-DM1)
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been approved
in the European Union (EU) as a monotherapy 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 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 (EC) follows
the positive
opinion of the Committee
for Medicinal Products for Human Use and is based on results from
the DESTINY-Breast03 Phase III trial, which were published
in The
New England Journal of Medicine.1 In
the trial, Enhertu reduced the risk of disease progression or
death by 72% versus trastuzumab emtansine (T-DM1) (hazard ratio
[HR] 0.28; 95% confidence interval [CI] 0.22-0.37; p<0.000001)
in patients with HER2-positive unresectable and/or metastatic
breast cancer previously treated with trastuzumab and a
taxane.
In Europe, more than 530,000 patients are diagnosed with breast
cancer each year.2 Approximately
one in five patients with breast cancer are considered
HER2-positive.3 Despite
initial treatment with trastuzumab, pertuzumab and a taxane,
patients with HER2-positive metastatic breast cancer will often
experience disease progression.4,5
Javier Cortés, MD, PhD, Head, International Breast Cancer
Center (IBCC), Barcelona, Spain, said: "This approval is an
important milestone for patients and clinicians in Europe, since
previously treated patients with HER2-positive metastatic breast
cancer typically experience disease progression in less than a year
with historical standard of care treatment. In the DESTINY-Breast03
trial, the time to progression was extended well beyond a year for
patients receiving Enhertu, illustrating the potential for this medicine to
set a new benchmark in the treatment of HER2-positive metastatic
breast cancer."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "With this approval, patients across Europe
with HER2-positive metastatic breast cancer will have the
opportunity to be treated with Enhertu even earlier in the treatment of their
disease, improving their chance for better outcomes beyond what we
can already offer patients treated in later-line settings. Today's
news is a further step in achieving our vision to continuously
bring the transformative potential of Enhertu to patients as early as possible in their
treatment to improve cancer outcomes."
Ken Keller, Global Head of Oncology Business, and President and
CEO, Daiichi Sankyo, Inc., said: "We believe there is a significant
need to transform outcomes for patients with HER2-positive
metastatic breast cancer in Europe. In DESTINY-Breast03, treatment
with Enhertu demonstrated superior progression-free
survival and a doubling of the response rate compared to another
HER2-directed ADC. With this approval we are now able to offer
patients with HER2-positive metastatic breast cancer another option
earlier in their treatment."
Additional results from the DESTINY-Breast03 Phase III trial showed
that in the secondary endpoint of overall survival (OS), there was
a strong trend towards improved OS with Enhertu (HR 0.55; 95% CI 0.36-0.86), however this
analysis is not yet mature and further follow-up is ongoing. Nearly
all patients (96.1%) treated with Enhertu were alive at nine months compared to 91.3%
of patients treated with T-DM1. Confirmed objective response rate
(ORR) was more than doubled in the Enhertu arm versus the T-DM1 arm (79.7% vs.
34.2%).
The safety of Enhertu has been evaluated in a pooled analysis of
573 patients across multiple tumour types who had received at least
one dose of Enhertu (5.4 mg/kg) in clinical trials. The most
common adverse reactions were nausea (77.0%), fatigue (57.2%),
vomiting (46.8%), alopecia (38.0%) and neutropenia (34.6%). Cases
of interstitial lung disease (ILD) or pneumonitis were reported in
12.0% of patients. Most ILD cases were Grade 1 (2.6%) and Grade 2
(7.3%). Grade 3 cases occurred in 0.7% of patients, no Grade 4
cases occurred, and Grade 5 cases occurred in 1.4% of
patients.
Based on the results of DESTINY-Breast03, the European Society for
Medical Oncology Clinical Practice Guidelines were updated in
October 2021 to recommend Enhertu for use as the preferred second-line therapy
for patients with HER2-positive metastatic breast cancer following
progression with a taxane and trastuzumab.6
As part of this approval, the EC has also extended the market
protection period for Enhertu in this setting by one extra year based on
the significant clinical benefit compared to existing approved
therapies.
Notes
Financial considerations
Following EU approval, an amount of $75m is due from AstraZeneca to
Daiichi Sankyo as a milestone payment in 2nd-line HER2-positive
metastatic breast cancer. The milestone will be capitalised as an
addition to the upfront payment made by AstraZeneca to Daiichi
Sankyo in 2019 and subsequent capitalised milestones, and will be
amortised through the profit and loss statement.
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 breast cancer
Breast cancer is the most common cancer and is one of the leading
causes of cancer-related deaths worldwide.7 More
than two million patients were diagnosed with breast cancer in
2020, with nearly 685,000 deaths globally.7 In
Europe, more than 530,000 patients are diagnosed with breast cancer
each year.2 Approximately
one in five patients with 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.8 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.9
Despite initial treatment with trastuzumab, pertuzumab and a
taxane, patients with HER2-positive metastatic breast cancer will
often experience disease progression.4,5 More
treatment options are needed to further delay progression and
extend survival.4,10,11
DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomised, open-label,
registrational Phase III trial evaluating the efficacy and safety
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 PFS based on
blinded independent central review. OS is a key secondary efficacy
outcome measure. Secondary efficacy endpoints include ORR, duration
of response and PFS based on investigator assessment.
DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia,
Europe, North America, Oceania and South America. Results from
DESTINY-Breast03 have been published in The
New England Journal of Medicine.1 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 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 also
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 (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 (GEJ) adenocarcinoma who have received a
prior trastuzumab-based regimen based on the results from the
DESTINY-Gastric01 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 are currently under review in China, Japan
and several other countries for the treatment of adult patients
with unresectable or metastatic HER2-positive breast cancer who
have received a prior anti-HER2-based regimen based on the results
from the DESTINY-Breast03 trial.
Enhertu is
under review in Europe for
the treatment of adult
patients with unresectable or metastatic
HER2-low (immunohistochemistry (IHC) 1+ or IHC
2+/ in-situ hybridisation (ISH)-negative) 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 from the
DESTINY-Breast04 trial. Patients with hormone receptor (HR)
positive breast cancer must additionally have received or be
ineligible for endocrine therapy.
Enhertu is also currently
under review in the US for the treatment of adult patients with
unresectable or metastatic non-small cell lung cancer (NSCLC) whose
tumours have a HER2 (ERBB2) mutation and who have received a prior
systemic therapy based on the results of the DESTINY-Lung01 trial,
and in Europe for the treatment of adult patients with locally
advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma
who have received a prior anti-HER2-based regimen based on the
DESTINY-Gastric01 and DESTINY-Gastric02 trials.
Enhertu was
granted Breakthrough Therapy
Designation in the US for
the treatment of adult patients with unresectable or metastatic
HER2-low (IHC 1+ or IHC 2+/ISH-negative) 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. Patients with HR-positive breast cancer
should additionally have received or be ineligible for endocrine
therapy.
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 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
that has been studied in HER2-negative early and 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 initial approvals 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. Cortes J, et al. Trastuzumab
Deruxtecan versus Trastuzumab Emtansine for Breast
Cancer. N Engl J
Med. 2022;
386:1143-1154.
2. Globocan 2020. Europe Fact Sheets.
Available at: https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf.
Last accessed: July 2022.
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. Nader-Marta
G, et al. How
we treat patients with metastatic HER2-positive breast
cancer. ESMO Open. 2022; 7:1.
6.
Gennari A, et al. ESMO Clinical Practice Guideline for the
diagnosis, staging and treatment of patients with metastatic breast
cancer. Available at:
https://www.annalsofoncology.org/article/S0923-7534(21)04498-7/pdf.
Last accessed: July 2022.
7. 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.
8. Iqbal N, et al. Human Epidermal
Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and
Therapeutic Implications. Mol Biol
Int.
2014;852748.
9. Pillai R, et al. HER2 mutations in
lung adenocarcinomas: A report from the Lung Cancer Mutation
Consortium. Cancer. 2017;1;123(21):4099-4105.
10. 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.
11. 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.
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 July 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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