TIDMAZN
RNS Number : 7384X
AstraZeneca PLC
23 December 2019
23 December 2019 07:00 GMT
Enhertu (trastuzumab deruxtecan) approved in the US for
HER2-positive unresectable or metastatic breast cancer following
two or more prior
anti-HER2 based regimens
Accelerated Approval of AstraZeneca and Daiichi Sankyo's Enhertu
based on the DESTINY-Breast01 trial that showed clinically
meaningful and durable responses
AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)
today announced that the US Food and Drug Administration (FDA) has
approved Enhertu (fam-trastuzumab deruxtecan-nxki) 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.
This indication is approved under Accelerated Approval based on
tumour response rate and duration of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in a confirmatory trial.
Enhertu is a HER2-directed antibody-drug conjugate (ADC) and the
FDA approval is based on the results of the registrational Phase II
trial DESTINY-Breast01 of Enhertu (5.4mg/kg) monotherapy in
patients with HER2-positive metastatic breast cancer. All patients
received prior trastuzumab, trastuzumab emtansine and 66% had prior
pertuzumab.
The Phase II trial results showed a confirmed objective response
rate of 60.3% (n=111, 95% CI 52.9-67.4) including a 4.3% complete
response rate (n=8) and a 56.0% partial response rate (n=103). A
median duration of response of 14.8 months (95% CI 13.8-16.9) was
demonstrated as of 1 August 2019.(1) In addition, a median
progression-free survival of 16.4 months (95% CI 12.7-not
estimable), based upon a median duration of follow up of 11.1
months, was recently presented at the San Antonio Breast Cancer
Symposium and published online in The New England Journal of
Medicine.(2)
José Baselga, Executive Vice President, Oncology R&D, said:
"Enhertu has shown impressive results in women with HER2-positive
metastatic breast cancer, with the majority of women benefiting
from treatment and the median duration of the response exceeding 14
months. With this first approval, we are proud to bring Enhertu to
patients with high unmet need and we look forward to further
exploring its potential in additional settings."
Antoine Yver, Executive Vice President and Global Head, Oncology
R&D, Daiichi Sankyo said: "The approval of Enhertu underscores
that this specifically engineered HER2-directed antibody-drug
conjugate is delivering on its intent to establish an important new
treatment for patients with HER2-positive metastatic breast cancer.
Since the beginning of our clinical trial programme four years ago,
we have focused on the opportunity to transform the treatment
landscape for patients with HER2-positive metastatic breast cancer,
and we are extremely proud of how quickly we delivered Enhertu to
patients in the US, as Enhertu represents one of the
fastest-developed biologics in oncology."
The safety of Enhertu has been evaluated in a pooled analysis
from both the Phase II trial DESTINY-Breast01 and the earlier Phase
I trial among a total of 234 patients with unresectable or
metastatic HER2-positive breast cancer who received at least one
dose of Enhertu (5.4mg/kg).
The most common adverse reactions (greater than or equal to 20%
of patients) were nausea, fatigue, vomiting, alopecia and
constipation. Interstitial lung disease (ILD)/pneumonitis occurred
in 9% of patients. Fatal outcomes due to ILD/pneumonitis occurred
in six patients (2.6%) - two deaths previously reported in the
Phase I trial and four deaths previously reported in the Phase II
trial DESTINY-Breast01. Following an initial ILD management
programme already in place, a further monitoring, management and
educational campaign on ILD/pneumonitis was launched in 2019.
Patients and physicians should be aware of ILD/pneumonitis and
patients should be actively screened and monitored for potential
signs and symptoms. If ILD/pneumonitis is identified, it should be
managed with dose modification and steroid treatment according to
management guidelines.(2)
A regulatory submission for the treatment of patients with
HER2-positive metastatic breast cancer has also been made to
Japan's Ministry of Health, Labour and Welfare based on the
DESTINY-Breast01 and Phase I trials.
AstraZeneca and Daiichi Sankyo are exploring the further
potential of Enhertu in HER2-breast cancer with three ongoing Phase
III trials.
Financial considerations
Following US approval, an amount of $125m is due from
AstraZeneca to Daiichi Sankyo as the first milestone payment in
HER2-positive breast cancer. Upon approval, this will be
capitalised together with the upfront payment already made earlier
in the year 2019.
Future sales of Enhertu in the US will be recognised by Daiichi
Sankyo. AstraZeneca will report its share of gross profit margin
from the sales in the US as collaboration revenue in the Company's
financial statements. For further details on the financial
arrangements, please consult the announcement of the collaboration
agreement from March 2019.
About HER2-positive breast cancer
Approximately one in five breast cancers are HER2-positive.(3,4)
Despite recent improvements and approvals of new medicines, there
remains significant unmet needs for patients with HER2-positive
metastatic breast cancer.(5,6) This disease remains incurable with
patients eventually progressing after available
treatments.(5,6)
About HER2
HER2 is a tyrosine kinase receptor growth-promoting protein
found on the surface of some cancer cells that is associated with
aggressive disease and poor prognosis in patients with breast
cancer.(7) To be considered HER2-positive, tumour cancer cells are
usually tested by one of two methods: immunohistochemistry (IHC) or
fluorescent in situ hybridisation (FISH). IHC test results are
reported as: 0, IHC 1+, IHC 2+, or IHC 3+.(3) A finding of IHC 3+
and/or FISH amplification is considered positive.(3)
About DESTINY-Breast01
DESTINY-Breast01 is a registrational Phase II, single-arm,
open-label, global, multicentre, two-part trial evaluating 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 is
objective response rate, as determined by independent central
review. Secondary objectives include duration of response, disease
control rate, clinical benefit rate, progression-free survival and
overall survival. Enrolment into DESTINY-Breast01 was completed in
September 2018 with 184 patients at more than 100 sites
globally.
About Enhertu
Enhertu (fam-trastuzumab deruxtecan-nxki in the US only;
trastuzumab deruxtecan outside the US) is the lead product in the
ADC Franchise of the Daiichi Sankyo Cancer Enterprise 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.
About Enhertu clinical development
A comprehensive development programme is underway globally with
five registrational trials in HER2-expressing metastatic breast and
gastric cancers including a trial in patients with metastatic
breast cancer and low levels of HER2 expression. Phase II trials
are underway for HER2-expressing advanced colorectal cancer, as
well as metastatic non-squamous HER2-overexpressing or HER2-mutated
non-small cell lung cancer. Trials in combination with other
anticancer treatments, such as immunotherapy, are also
underway.
About the collaboration between AstraZeneca and Daiichi
Sankyo
In March 2019, AstraZeneca and Daiichi Sankyo entered into a
global collaboration to jointly develop and commercialise Enhertu
worldwide, except in Japan where Daiichi Sankyo maintains exclusive
rights. Daiichi Sankyo is solely responsible for manufacturing and
supply.
About 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 at
least six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologic medicines in
development, the Company is committed to advance oncology as a key
growth driver for AstraZeneca focused on lung, ovarian, breast and
blood cancers. In addition to AstraZeneca's main capabilities, the
Company is actively pursuing innovative partnerships and
investments that accelerate the delivery of our strategy, as
illustrated by the investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody-Drug Conjugates - 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.
About AstraZeneca
AstraZeneca (LSE/STO/NYSE: 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 and Metabolism, and Respiratory.
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.
Media Relations
Gonzalo Viña +44 203 749 5916
Rob Skelding Oncology +44 203 749 5821
Rebecca Einhorn Oncology +1 301 518 4122
Matt Kent BioPharmaceuticals +44 203 749 5906
Jennifer Hursit Other +44 203 749 5762
Christina Malmberg Hägerstrand Sweden +46 8 552 53 106
Michele Meixell US +1 302 885 2677
Investor Relations
Thomas Kudsk Larsen +44 203 749 5712
Henry Wheeler Oncology +44 203 749 5797
Christer Gruvris BioPharmaceuticals (Cardiovascular, Metabolism) +44 203 749 5711
BioPharmaceuticals (Renal) Environmental, Social and
Nick Stone Governance +44 203 749 5716
BioPharmaceuticals (Respiratory)
Josie Afolabi Other medicines +44 203 749 5631
Finance
Craig Marks Fixed income +44 7881 615 764
Corporate access
Jennifer Kretzmann Retail investors +44 203 749 5824
US toll-free +1 866 381 72 77
References
1. ENHERTU(R) [fam-trastuzumab deruxtecan-nxki] US prescribing
information; 2019.
2. Modi, S., et. al. Trastuzumab Deruxtecan in Previously
Treated HER2-Positive Breast Cancer. NEJM. December 11, 2019.
DOI:10.1056/NEJMoa1914510.
3. Tandon A, et al. HER-2/neu Oncogene Protein and Prognosis in
Breast Cancer. J Clin Oncol. 1989;7(8):1120-8.
4. Sledge G, et al. Past, Present, and Future Challenges in
Breast Cancer Treatment. J Clin Oncol. 2014;32(19):1979-1986.
5. 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.
6. National Comprehensive Cancer Network (NCCN). NCCN
Guidelines. Breast Cancer. Available at https://nccn.org. Accessed
December 2019.
7. American Cancer Society. Breast Cancer HER2 Status. Available
at
https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html.
Accessed December 2019.
Adrian Kemp
Company Secretary
AstraZeneca PLC
This information is provided by RNS, the news service of the
London Stock Exchange. RNS is approved by the Financial Conduct
Authority to act as a Primary Information Provider in the United
Kingdom. Terms and conditions relating to the use and distribution
of this information may apply. For further information, please
contact rns@lseg.com or visit www.rns.com.
END
MSCCKDDNNBDDKBB
(END) Dow Jones Newswires
December 23, 2019 02:00 ET (07:00 GMT)
Astrazeneca (LSE:AZN)
Historical Stock Chart
From Feb 2024 to Mar 2024
Astrazeneca (LSE:AZN)
Historical Stock Chart
From Mar 2023 to Mar 2024