a8765n
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 October
2021
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu granted BTD for breast cancer
4 October 2021 07:00 BST
Enhertu granted Breakthrough Therapy Designation in
US for patients with HER2-positive metastatic breast cancer treated
with one or more prior anti-HER2-based regimens
Based on ground-breaking DESTINY-Breast03 results where Enhertu
reduced the risk of disease progression or death by 72% vs.
trastuzumab emtansine (T-DM1)
Enhertu has now been granted four Breakthrough
Therapy Designations, including two in breast cancer
The Food and Drug Administration (FDA) has
granted Enhertu (trastuzumab deruxtecan), Breakthrough
Therapy Designation (BTD) in the US 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 HER2-directed antibody drug conjugate
(ADC) jointly developed by AstraZeneca and Daiichi Sankyo Company,
Limited (hereafter, Daiichi Sankyo).
The FDA granted BTD based on data from the DESTINY-Breast03 Phase
III trial presented during
the European Society for Medical Oncology (ESMO) Congress
2021. This is the second BTD for Enhertu in breast cancer and now brings the total
number of BTDs to four for this medicine.
The US FDA's BTD is designed to accelerate the development and
regulatory review of potential new medicines that are intended to
treat a serious condition and address a significant unmet medical
need. The new medicine needs to have shown encouraging preliminary
clinical results that demonstrate substantial improvement on a
clinically significant endpoint over available
medicines.
Breast cancer remains the most common cancer worldwide, with more
than two million cases diagnosed in 2020, resulting in nearly
685,000 deaths globally.1 Approximately
one in five cases of breast cancer are considered
HER2-positive.2
Despite initial treatment with trastuzumab and a taxane, patients
with HER2-positive metastatic breast cancer will often experience
disease progression.3 More
effective options are needed to further delay progression and
extend survival.3-5
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "This is an important step in
bringing Enhertu as a potential new option in earlier lines
of treatment for HER2-positive metastatic breast cancer, given the
urgent need to improve outcomes. This recognition by the FDA
underscores the transformative possibility
of Enhertu seen with the remarkable DESTINY-Breast03
results presented at ESMO just two weeks ago."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "By
granting a fourth Breakthrough Therapy Designation
to Enhertu, the FDA continues to recognise the significant
potential of this medicine across multiple HER2-targetable tumours.
With the unprecedented data recently reported from the
DESTINY-Breast03 trial, we look forward to working closely with the
FDA to bring Enhertu to patients who have been previously treated
for HER2-positive metastatic breast cancer as soon as
possible."
In DESTINY-Breast03, Enhertu demonstrated a 72% reduction in the risk of
disease progression or death compared to T-DM1 (hazard ratio [HR]
0.28; 95% confidence interval [CI] 0.22-0.37;
p=7.8x10-22)
in patients with HER2-positive unresectable and/or metastatic
breast cancer previously treated with trastuzumab and a taxane.
Nearly all patients treated with Enhertu were alive at one year (94.1%) compared to
85.9% of patients treated with T-DM1. Confirmed objective response
rate (ORR) more than doubled in the Enhertu arm versus the T-DM1 arm (79.7% vs. 34.2%).
The safety profile of Enhertu was consistent with previous clinical
trials, with no new safety concerns identified and no Grade 4 or 5
treatment-related interstitial lung disease
events.
Previous BTDs for Enhertu were in late-line HER2-positive metastatic
breast cancer in 2017 and HER2-mutant metastatic non-small cell
lung cancer (NSCLC) and HER2-positive metastatic gastric
cancer in 2020.
Enhertu is approved 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 in the US,
Japan, the EU and several other countries based on the results from
the DESTINY-Breast01 trial.
Enhertu is being further
assessed in a comprehensive clinical development programme
evaluating efficacy and safety across multiple HER2-targetable
cancers, including breast, gastric, lung and colorectal
cancers.
HER2-positive breast cancer
Breast cancer remains the most common cancer and is one of the
leading causes of cancer-related deaths in women
worldwide.1 More
than two million patients with breast cancer were diagnosed in
2020, resulting in nearly 685,000 deaths
globally.1 Approximately
one in five cases of breast cancer are considered
HER2-positive.2
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.6 HER2
protein overexpression may occur as a result of HER2 gene
amplification and is often associated with aggressive disease and a
poor prognosis in breast cancer.7
Despite initial treatment with trastuzumab and a taxane, people
with HER2-positive metastatic breast cancer will often experience
disease progression.3 More
effective options are needed to further delay progression and
extend survival.3-5
DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label,
registrational Phase III trial evaluating the safety and efficacy
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
progression-free survival (PFS) based on blinded independent
central review. Secondary efficacy endpoints include overall
survival, objective response rate, duration of response, PFS based
on investigator assessment and safety.
DESTINY-Breast03 enrolled approximately 500 patients at
multiple sites in Asia, Europe, North America, Oceania and South
America. 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 Canada, the EU, Israel, Japan, the UK and the US 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
results from the DESTINY-Breast01 trial.
Enhertu (6.4mg/kg) is also
approved in Israel, Japan and the US for the treatment of adult
patients with locally advanced or metastatic HER2-positive gastric
or gastroesophageal junction 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.
Enhertu was highlighted in
the Clinical Cancer Advances 2021 report as one of two significant
advancements in the "ASCO Clinical Advance of the Year: Molecular
Profiling Driving Progress in GI Cancers", based on data from both
the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of
the targeted therapy advances of the year in NSCLC, based on the
interim results of the HER2-mutated cohort of the DESTINY-Lung01
trial.
Daiichi Sankyo collaboration
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
SERD and potential new medicine camizestrant.
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.
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 Imfinzi (durvalumab) in combination with other
oncology medicines, including Lynparza and Enhertu, investigating 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.
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.
2.
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.
3.
Barok M, et al. Trastuzumab emtansine: mechanism of action and
drug resistance. Breast Cancer
Res. 2014;
16(2):209.
4.
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.
5.
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.
6.
Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2)
in Cancers: Overexpression and Therapeutic
Implications. Mol Biol
Int.
2014;852748.
7.
Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report
from the Lung Cancer Mutation Consortium. Cancer. 2017;1;123(21):4099-4105.
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:
4 October
2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|