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
2019
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu (trastuzumab deruxtecan) approved in the US for
HER2-positive unresectable or metastatic breast cancer following
two or more prior
anti-HER2 based regimens
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.
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References
1. ENHERTU® [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
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:
23 December
2019
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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