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 July 2022
Commission
File Number: 001-11960
AstraZeneca PLC
Enhertu
granted Priority Review for HER2-low mBC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu granted Priority Review for HER2-low mBC
25 July 2022 07:00 BST
Enhertu granted
Priority Review in the US for
patients with HER2-low metastatic breast cancer
Based on DESTINY-Breast04 results which showed AstraZeneca and
Daiichi Sankyo's Enhertu is the first HER2-directed therapy to
demonstrate a survival benefit in this population
Application being evaluated under FDA Real-Time Oncology Review and
Project Orbis
AstraZeneca and Daiichi Sankyo have received notification of
acceptance of the supplemental Biologics License Application (sBLA)
of Enhertu (trastuzumab deruxtecan) for the treatment
of adult patients in the US with unresectable or metastatic
HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ
hybridisation [ISH]-negative) breast cancer who have received a
prior therapy in the metastatic setting. The application has
been granted Priority Review.
Enhertu is a specifically
engineered HER2-directed antibody drug conjugate (ADC) being
jointly developed and commercialised by AstraZeneca and Daiichi
Sankyo.
The Food and Drug Administration (FDA) grants Priority Review to
applications for medicines that, if approved, would offer
significant improvements over available options by demonstrating
safety or efficacy improvements, preventing serious conditions or
enhancing patient compliance. The Prescription Drug User Fee Act
date, the FDA action date for their regulatory decision, is during
the fourth quarter of 2022.
The sBLA is being reviewed under the Real-Time Oncology Review
(RTOR) programme and Project Orbis, two initiatives of the FDA
which are designed to bring safe and effective cancer treatments to
patients as early as possible. RTOR allows the FDA to review
components of an application before submission of the complete
application. Project Orbis provides a framework for concurrent
submission and review of oncology medicines among participating
international partners.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "The data from DESTINY-Breast04 represent
the first time a HER2-targeted therapy has shown a survival benefit
in patients with HER2-low metastatic breast cancer. For more than
two decades, only patients with HER2-positive breast cancer have
been able to benefit from HER2-targeted therapies. If
approved, Enhertu will redefine how we classify and treat
metastatic breast cancer, enabling patients whose tumours have
lower levels of HER2 expression the opportunity to benefit from a
HER2-directed therapy."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "The
results seen in the DESTINY-Breast04 trial represent a significant
advance and reinforce the potential for Enhertu to become a new standard of care for
patients with previously treated HER2-low metastatic breast cancer.
The prioritisation of this application by the FDA and inclusion in
both the Real-Time Oncology Review and Project Orbis initiatives
support the importance of these data, and we look forward to
working with the FDA to potentially bring Enhertu to patients with HER2-low metastatic breast
cancer as quickly as possible."
The sBLA is based on data from the DESTINY-Breast04 Phase
III trial that were presented at the presidential plenary
session of the 2022 American Society of Clinical Oncology Annual
Meeting and simultaneously
published in The
New England Journal of Medicine.1
In the trial, Enhertu demonstrated superior and clinically
meaningful efficacy in progression-free survival (PFS) and overall
survival (OS) in previously treated patients with HER2-low
metastatic breast cancer with hormone receptor (HR)-positive or
HR-negative disease versus standard of care physician's choice of
chemotherapy.
The safety profile of Enhertu was consistent with previous clinical trials
with no new safety concerns identified. Interstitial lung disease
or pneumonitis rates were consistent with that observed in
late-line HER2-positive breast cancer trials
of Enhertu, as determined by an independent adjudication
committee. The majority (10%) were primarily low Grade (Grade 1 or
2) with five Grade 3 (1.3%), no Grade 4 and three Grade 5 (0.8%)
events reported.
This Priority Review follows receipt of Breakthrough Therapy
Designation (BTD) in the US in April 2022 in metastatic HER2-low breast
cancer, the fifth BTD in the US for Enhertu.
Regulatory reviews for Enhertu in the HER2-low patient population are also
underway in the European Union (EU) and Japan, and Enhertu is already approved in the US, the EU and
many other countries across the globe for patients with previously
treated HER2-positive (IHC 3+ or IHC 2+/ISH-positive) metastatic
breast cancer.
Notes
Breast cancer and HER2 expression
Breast cancer is the most common cancer and is one of the leading
causes of cancer-related deaths worldwide
and in the
US.2,3 More
than two million cases of breast cancer were diagnosed in 2020
resulting in nearly 685,000 deaths
globally.2 In
the US, more than 290,000 new cases are expected to be diagnosed in
2022, resulting in more than 43,000 deaths.4
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, and is one of many biomarkers
expressed in breast cancer tumours.5 HER2
expression is currently defined as either positive or negative, and
is determined by an IHC test which estimates the amount of HER2
protein on a cancer cell, and/or an ISH test, which counts
the copies of the HER2 gene in cancer
cells.5,6
HER2-positive cancers are defined as IHC 3+, IHC 2+/ISH+, and
HER2-negative cancers are currently defined as IHC 0, IHC 1+ or IHC
2+/ISH-.5 Approximately
half of all patients with breast cancer have tumours with low HER2
expression, with a HER2 IHC score of 1+, or a HER2 IHC score of 2+
in combination with a negative ISH test, an expression level not
currently eligible for HER2-targeted therapy.7-10 Low
HER2 expression occurs in both HR-positive and HR-negative
disease.11
DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label, Phase III
trial evaluating the efficacy and safety
of Enhertu (5.4mg/kg)
versus physician's choice of chemotherapy (capecitabine, eribulin,
gemcitabine, paclitaxel or nab-paclitaxel) in patients with
HR-positive or HR-negative, HER2-low unresectable and/or metastatic
breast cancer previously treated with one or two prior lines of
chemotherapy. Patients were randomised 2:1 to receive
either Enhertu or chemotherapy.
The primary endpoint of DESTINY-Breast04 is PFS in patients with
HR-positive disease based on blinded independent central review
(BICR). Key secondary endpoints include PFS based on BICR in all
randomised patients (HR-positive and HR-negative disease), OS in
patients with HR-positive disease and OS in all randomised patients
(HR-positive and HR-negative disease). Other secondary endpoints
include PFS based on investigator assessment, objective response
rate based on BICR and on investigator assessment, duration of
response based on BICR and safety.
DESTINY-Breast04 enrolled 557 patients at multiple sites in Asia,
Europe and North 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 more than 30 countries for the treatment of
adult patients with unresectable or metastatic HER2-positive breast
cancer who have received a prior anti-HER2-based
regimen either in the metastatic setting, or in the
neoadjuvant or adjuvant setting and have developed disease
recurrence during or within six months of completing
therapy, based on results from the DESTINY-Breast03
trial.
Enhertu (5.4mg/kg) is
approved in several countries 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 based on
the results from the DESTINY-Breast01
trial.
Enhertu (6.4mg/kg) is
approved in several countries for the treatment of adult patients
with locally advanced or metastatic HER2-positive gastric or
gastroesophageal junction (GEJ) 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.
Regulatory applications for Enhertu are currently under review in China, Japan
and several other countries for the treatment of adult patients
with HER2-positive unresectable or metastatic breast cancer who
have received a prior anti-HER2-based regimen based on the results
from the DESTINY-Breast03 trial.
Enhertu is under review in
Europe and Japan for the treatment of adult patients with
unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast
cancer who have received a prior systemic therapy in the metastatic
setting or developed disease recurrence during or within six months
of completing adjuvant chemotherapy, based on the results from the
DESTINY-Breast04 trial. Patients with HR-positive breast cancer
must additionally have received or be ineligible for endocrine
therapy.
Enhertu is under review in
the US for the treatment of adult patients with unresectable or
metastatic non-small cell lung cancer whose tumours have a HER2
(ERBB2) mutation and who have received a prior systemic therapy
based on the results from the DESTINY-Lung01 trial, and in Europe
for the treatment of adult patients with locally advanced or
metastatic HER2-positive gastric or GEJ adenocarcinoma who have
received a prior anti-HER2-based regimen based on the
DESTINY-Gastric01 and DESTINY-Gastric02 trials.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to
as 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 the manufacturing and
supply of Enhertu and datopotamab
deruxtecan.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology,
AstraZeneca is challenging and redefining the current clinical
paradigm for how breast cancer is classified and treated to deliver
even more 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
selective oestrogen receptor degrader (SERD) and potential new
medicine camizestrant.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option
that has been studied in HER2-negative early and 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, evaluating 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. Modi S, et al. Trastuzumab
Deruxtecan in Previously Treated HER2-Low Advanced Breast
Cancer. N Engl J
Med. 2022;387:9-20.
2. 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.
3.
Centers for Disease Control and Prevention. Available at:
https://gis.cdc.gov/Cancer/USCS/#/AtAGlance/. Accessed July
2022.
4.
American Cancer Society. Cancer Facts & Figures 2022. Available
at:
https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html.
Accessed July 2022.
5. Iqbal N, et al. Human Epidermal
Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and
Therapeutic Implications. Mol Biol
Int. 2014;852748.
6. Wolff
A, et al. Human Epidermal Growth Factor Receptor 2
Testing in Breast Cancer: American Society of Clinical
Oncology/College of American Pathologists Clinical Practice
Guideline Focused Update. Arch Pathol Lab
Med.
2018;142(11):1364-1382.
7. Schalper K, et al. A
retrospective population-based comparison of HER2
immunohistochemistry and fluorescence in situ hybridization in
breast carcinomas. Arch Pathol Lab
Med. 2014;138:213-219.
8. 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.
9. Schettini F, et al. Clinical,
pathological, and PAM50 gene expression features of HER2-low breast
cancer. npj Breast
Cancer. 2021;7:1;https://doi.org/10.1038/s41523-020-00208-2.
10. Denkert C, et al. Clinical and
molecular characteristics of HER2-low-positive breast cancer:
pooled analysis of individual patient data from four prospective,
neoadjuvant clinical trials. 2021. Lancet
Oncol;22:1151-61.
11. Miglietta F, et al. Evolution of
HER2-low expression from primary to recurrent breast
cancer. NPJ Breast
Cancer.
2021;7:137;10.1038/s41523-021-00343-4.
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:
25 July 2022
|
|
By: /s/
Adrian Kemp
|
|
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Name:
Adrian Kemp
|
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Title:
Company Secretary
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