TIDMAZN
RNS Number : 2821M
AstraZeneca PLC
20 January 2021
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
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