a2825m
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 2021
Commission
File Number: 001-11960
AstraZeneca PLC
1
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Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu approved in the EU for breast
cancer
20 January 2021 07:00 GMT
Enhertu approved in the EU for the
treatment
of HER2-positive metastatic breast cancer
Approval based on DESTINY-Breast01 Phase II trial which showed
clinically meaningful and durable responses in patients with
previously treated disease
AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi
Sankyo)'s Enhertu (trastuzumab deruxtecan) has been granted
conditional approval 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 two or more prior
anti-HER2-based regimens.
In Europe, approximately 531,000 cases of breast cancer in women
are diagnosed annually, with an estimated one in five cases being
HER2-positive.1-3 The
impact of the disease is significant, with breast cancer
responsible for more than 141,000 deaths per year in
Europe.1
The approval by the European Commission was based on positive
results from the single-arm DESTINY-Breast01 Phase II trial, in
which Enhertu showed clinically meaningful and durable
antitumour activity in patients with HER2-positive metastatic
breast cancer who had received two or more prior anti-HER2-based
regimens.4 It
follows the December 2020 recommendation for
approval by the Committee for Medicinal Products for Human Use of
the European Medicines Agency, which reviewed the application under
its accelerated assessment procedure.
Professor Fabrice André, Head of Research, Department of
Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France,
said: "One in five women with breast cancer have HER2-positive
disease and those with previously treated metastatic disease often
progress quickly. One of the biggest challenges in this setting has
been identifying treatments that produce a durable
response. The DESTINY-Breast01 trial showed a breadth, depth
and durability of response not previously seen in this patient
population."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "Enhertu is already transforming outcomes for
patients with HER2-positive metastatic breast cancer in the US and
Japan, and this approval enables us to bring the benefits of this
medicine to patients in the EU. We will continue to explore the
potential of Enhertu in this setting, as well as in earlier lines
of treatment and stages of disease, with the ambition of improving
the lives of patients with HER2-targetable breast
cancer."
Gilles Gallant, Senior Vice President, Global Head, Oncology
Development, Oncology R&D, Daiichi Sankyo, said: "This
expedited review underscores the practice-changing potential
of Enhertu for patients in the metastatic
setting. Enhertu is the first-ever new medicine to be
approved in breast cancer in Europe on the basis of Phase II
single-arm data, and one of the fastest accelerated assessment
procedures for an application in oncology."
In the DESTINY-Breast01 Phase II trial, after a median follow-up of
20.5 months, Enhertu showed a confirmed objective response rate
(ORR) of 61.4%, including a 6.5% complete response rate and a 54.9%
partial response rate, and an estimated median duration of response
(DoR) of 20.8 months for patients with HER2-positive metastatic
breast cancer who had received at least two previous lines of
therapy.4
The analysis was presented during the 2020 San Antonio
Breast Cancer Symposium. An
earlier analysis with a median follow-up of 11.1 months was
published in The
New England Journal of Medicine in February 2020.5
The safety of Enhertu has been evaluated in a pooled analysis of
234 patients with unresectable or metastatic HER2-positive breast
cancer who received at least one dose of Enhertu 5.4mg/kg in clinical trials. The most common
adverse reactions were nausea, fatigue, vomiting, alopecia,
constipation, decreased appetite, anaemia, neutropenia, diarrhoea,
thrombocytopenia, cough, leukopenia and headache. Cases of
interstitial lung disease (ILD) or pneumonitis, were reported in
15.0% of patients, and in 2.6% of patients, ILD led to
death.
Enhertu (5.4mg/kg) is
approved in the US under accelerated approval, and in Japan under
the conditional early approval system 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 the metastatic setting based on the DESTINY-Breast01 Phase II
trial. It is also approved in the US and Japan for the treatment of
patients with HER2-positive unresectable advanced or recurrent
gastric cancer that has progressed after a trastuzumab-containing
regimen based on the DESTINY-Gastric01 Phase II
trial.
Enhertu is being further
assessed in several ongoing Phase III breast cancer trials as
part of a broad development programme, including DESTINY-Breast02,
a confirmatory trial in 3rd-line HER2-positive metastatic breast
cancer, and DESTINY-Breast03, as a 2nd-line treatment.
DESTINY-Breast04 is testing Enhertu in patients with metastatic breast cancer
and low expression of HER2; and DESTINY-Breast05 is
evaluating Enhertu as an adjuvant treatment of patients with
high-risk HER2-positive early breast cancer. Additional ongoing
trials are testing Enhertu in combination with other anti-cancer
medicines in HER2-positive and HER2-low metastatic breast
cancer.
Financial considerations
Following EU approval, an amount of $75m is due from AstraZeneca to
Daiichi Sankyo as a milestone payment for HER2-positive breast
cancer. In AstraZeneca, the milestones paid will be capitalised as
an addition to the upfront payment made in 2019 and subsequent
capitalised milestones and amortised through the profit and
loss.
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.
For further details on the financial arrangements, please consult
the collaboration agreement from March 2019.
HER2-positive breast cancer
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours, including breast
cancer. HER2 overexpression may be associated with a specific HER2
gene alteration known as HER2 amplification and is often associated
with aggressive disease and a poor prognosis in breast
cancer.6
There remain significant unmet clinical needs for patients with
HER2-positive metastatic breast cancer. The disease remains
incurable with patients eventually progressing after currently
available treatment options.7,8
DESTINY-Breast01
DESTINY-Breast01 was a single-arm, open-label, global, multicentre,
two-part Phase II trial testing the safety and efficacy
of Enhertu in patients with HER2-positive unresectable
and/or metastatic breast cancer previously treated with trastuzumab
emtansine. The primary endpoint of the trial was ORR, as determined
by independent central review. Secondary objectives included DoR,
disease control rate, clinical benefit rate, progression-free
survival and overall survival.
Enhertu
Enhertu (trastuzumab
deruxtecan; fam-trastuzumab deruxtecan-nxki in the
US) is a HER2-directed antibody drug conjugate
(ADC). It is the lead ADC in the oncology portfolio of Daiichi
Sankyo and the most advanced programme in AstraZeneca's ADC
scientific platform.
ADCs are targeted cancer medicines that deliver cytotoxic
chemotherapy ('payload') to cancer cells via a linker attached to a
monoclonal antibody that binds to a specific target expressed on
cancer cells. Enhertu is comprised of a humanised anti-HER2 IgG1
monoclonal antibody with the same amino acid sequence as
trastuzumab attached to a topoisomerase I inhibitor payload, an
exatecan derivative, via by a tetrapeptide-based cleavable
linker.
Development programme
A comprehensive development programme is underway globally, with
nine registrational trials evaluating the efficacy and safety
of Enhertu monotherapy across multiple HER2 cancers,
including breast, gastric and lung cancers. Trials in combination
with other anticancer treatments, such as immunotherapy, are also
underway.
In May 2020, Enhertu also received a Breakthrough Therapy
Designation for the treatment of patients with metastatic non-small
cell lung cancer whose tumours have a HER2 mutation and with
disease progression on or after platinum-based
therapy.
Daiichi Sankyo collaboration
Daiichi Sankyo and AstraZeneca entered a global collaboration to
jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and
datopotamab deruxtecan (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 SERD and
potential new medicine AZD9833. 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
state.
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 durvalumab in combination with other oncology
medicines, including Lynparza and Enhertu, assessing 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 has a deep-rooted heritage in oncology and offers a
quickly growing portfolio of new medicines that has the
potential to transform patients' lives and the Company's future.
With seven new medicines launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in
development, the Company is committed to advance oncology as a key
growth driver for AstraZeneca focused on lung, ovarian, breast and
blood cancers.
By harnessing the power of six scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage
Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies
- and by championing the development of personalised combinations,
AstraZeneca has the vision to redefine cancer treatment 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,
primarily for the treatment of diseases in three therapy areas -
Oncology, 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.
GLOBOCAN 2020 Breast Cancer Fact Sheet. World Health Organization.
Accessed January 2021.
2. DeKoven M, et al. Treatment pattern by hormone receptors and HER2
status in patients with metastatic breast cancer in the UK,
Germany, France, Spain and Italy (EU-5): results from a physician
survey. J Comp Eff
Res. 2012
Sep;1(5):453-63.
3. Sledge G, et al. Past, Present, and Future Challenges in Breast
Cancer Treatment. J Clin
Oncol. 2014;32(19):1979-1986.
4. European Medicines
Agency. Enhertu summary of product characteristics. Accessed
January 2021.
5. Modi, S et al. Trastuzumab deruxtecan in previously treated
HER2-positive breast cancer. N Engl J
Med. 2020;382:610-621; DOI:
10.1056/NEJMoa1914510.
6. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2)
in Cancers: Overexpression and Therapeutic
Implications. Mol Biol
Int.
2014;852748.
7. de Melo Gagliato
D, et
al. Mechanisms of resistance
and sensitivity to anti-HER2 therapies in HER2+ breast
cancer. Oncotarget. 2016;7(39):64431-46.
8.
National Comprehensive Cancer Network (NCCN). NCCN Guidelines
Version 3.2020. Breast Cancer. December 2020.
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:
20 January 2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|