a1546x
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 August 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza approved in Japan for early breast cancer
25 August 2022 07:00 BST
Lynparza approved
in Japan as adjuvant treatment for patients
with BRCA-mutated HER2-negative high-risk early breast
cancer
First and only approved medicine targeting
BRCA mutations in early breast cancer
AstraZeneca and MSD's Lynparza (olaparib) has been approved in Japan for
the adjuvant treatment of patients with BRCA-mutated (BRCAm),
HER2-negative early breast cancer at high risk of
recurrence.
This approval by the Japanese Ministry of Health, Labour, and
Welfare was based on
results from the OlympiA
Phase III trial published
in The
New England Journal of Medicine in
June 2021.1 In
the trial, Lynparza demonstrated a statistically significant and
clinically meaningful improvement in invasive disease-free survival
(iDFS), reducing the risk of invasive breast cancer recurrences,
new cancers, or death by 42% versus placebo (based on a hazard
ratio [HR] of 0.58; 99.5% confidence interval [CI] 0.41-0.82;
p<0.0001).
Lynparza also
demonstrated a statistically significant and clinically meaningful
improvement in overall
survival, reducing the risk of
death by 32% versus placebo (based on an HR of 0.68; 98.5%
CI 0.47-0.97;
p=0.009). The safety and tolerability profile
of Lynparza in this trial was in line with that observed
in prior clinical trials.
Breast cancer is the most diagnosed cancer worldwide with an
estimated 2.3 million patients diagnosed in
2020.2 In
Japan, an estimated 95,000 people will be diagnosed with breast
cancer in 2022, and over 15,000 will die from the
disease.3,4 Out
of the approximately 80% of patients with HER2-negative breast
cancer, about 11% have BRCA mutations.5,6
Professor Andrew Tutt, Global Chair of the OlympiA Phase III trial
and Professor of Oncology at The Institute of Cancer Research,
London, and King's College London, said: "Today's
approval marks a new era of care for patients in Japan. For
patients with high-risk early-stage breast cancer, including those
with germline BRCA mutations, recurrence rates remain unacceptably
high, with more than one in four of these patients seeing their
cancer return following surgery and systemic treatment. Today's
approval offers eligible patients in Japan an effective and
targeted treatment that improves survival and helps to prevent
cancer recurrence."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "Today's approval marks a significant leap
forward for breast cancer patients in Japan, where it is the most
commonly diagnosed cancer among women. Patients with BRCA mutations
have high rates of disease recurrence and lower survival,
and Lynparza has been shown to significantly reduce both
the risk of recurrence and death. We hope this approval sets a new,
much-needed standard of care for these early breast cancer patients
in Japan."
Dr Eliav Barr, Senior Vice President, Head of Global Clinical
Development and Chief Medical Officer, MSD Research Laboratories,
said: "With this approval, Lynparza becomes the first and only PARP inhibitor
available for patients with BRCA-mutated HER2-negative early breast
cancer in Japan. This further reinforces the critical need to
conduct BRCA testing at the point of diagnosis so that all eligible
patients can be identified."
In March 2022, Lynparza was approved in
the US for the treatment of germline BRCAm (gBRCAm), HER2-negative
high-risk early breast cancer, followed by approval in
the EU in August 2022 based on the results of the OlympiA Phase III
trial. Lynparza is also approved in the US, EU, Japan, and
many other countries for the treatment of patients with gBRCAm,
HER2-negative, metastatic breast cancer previously treated with
chemotherapy based on results from the OlympiAD Phase III trial. In
the EU, this indication also includes patients with locally
advanced breast cancer.
Notes
Early breast cancer
Early breast cancer is defined as cancer confined to the breast
with or without regional lymph node involvement, and the absence of
distant metastatic disease.7,8 In
Japan, breast cancer is both the most commonly diagnosed cancer
overall and the most prevalent cancer among
women.9 Over
90% of breast cancer patients in Japan are diagnosed with early
disease.10 In
2020, breast cancer accounted for an estimated 2.3 million new
cases and approximately 700,000 deaths
worldwide.2 Despite
advancements in the treatment of early breast cancer, up to 30% of
patients with high-risk clinical and/or pathologic features recur
within the first few years and patients with gBRCA mutations are
more likely to be diagnosed at a younger age than those without
these mutations.11,12
Breast cancer is one of the most biologically diverse tumour types
with various factors fuelling its development and
progression.13 The
discovery of biomarkers in the development of breast cancer has
greatly impacted scientific understanding of the
disease.14
OlympiA
OlympiA is a Phase III, double-blind, parallel group,
placebo-controlled, multicentre trial testing the efficacy and
safety of Lynparza tablets versus placebo as adjuvant treatment
in patients with gBRCAm, high-risk HER2-negative early breast
cancer, who have completed definitive local treatment and
neoadjuvant or adjuvant chemotherapy.15
The primary endpoint of the trial was iDFS defined as time from
randomisation to date of first locoregional or distant recurrence
or new cancer or death from any cause.1
The OlympiA Phase III trial is led by the Breast International
Group in partnership with the Frontier Science & Technology
Research Foundation, NRG Oncology, the US National Cancer
Institute, AstraZeneca and MSD. The trial is sponsored by NRG
Oncology in the US and by AstraZeneca outside the US.
BRCA
BRCA1 and BRCA2 are human genes that produce proteins responsible
for repairing damaged DNA and play an important role maintaining
the genetic stability of cells.11 When
either of these genes is mutated or altered such that its protein
product either is not made or does not function correctly, DNA
damage may not be repaired properly, and cells become unstable. As
a result, cells are more likely to develop additional alterations
that can lead to cancer. Cancers with BRCA mutations are more
likely to be sensitive to PARP inhibitors
including Lynparza.16-19
Lynparza
Lynparza (olaparib)
is a first-in-class PARP inhibitor and the first targeted treatment
to block DNA damage response (DDR) in cells/tumours harbouring a
deficiency in homologous recombination repair (HRR), such as those
with mutations in BRCA1 and/or BRCA2, or those where deficiency is
induced by other agents (such as new hormonal agents -
NHAs).
Inhibition of PARP proteins with Lynparza leads to the trapping of PARP bound to DNA
single-strand breaks, stalling of replication forks, their collapse
and the generation of DNA double-strand breaks and cancer cell
death.
Lynparza is
currently approved in a number of countries across PARP-dependent
tumour types with defects and dependencies in the DDR pathway
including maintenance treatment of platinum-sensitive relapsed
ovarian cancer and as both monotherapy and in combination with
bevacizumab for the 1st-line maintenance treatment of BRCA-mutated
(BRCAm) and homologous recombination repair deficient
(HRD)-positive advanced ovarian cancer, respectively; for gBRCAm,
HER2-negative metastatic breast cancer (in the EU and Japan this
includes locally advanced breast cancer); for gBRCAm, HER2-negative
high-risk early breast cancer (in the EU and US); for gBRCAm
metastatic pancreatic cancer; and HRR gene-mutated metastatic
castration-resistant prostate cancer (BRCAm only in the EU and
Japan).
Lynparza, which is being
jointly developed and commercialised by AstraZeneca and MSD, is the
foundation of AstraZeneca's industry-leading portfolio of potential
new medicines targeting DDR mechanisms in cancer
cells.
The AstraZeneca and MSD strategic oncology
collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth,
NJ, US, known as MSD outside the US and Canada, announced a global
strategic oncology collaboration to co-develop and
co-commercialise Lynparza,
the world's first PARP inhibitor, and Koselugo (selumetinib),
a mitogen-activated protein kinase (MEK) inhibitor, for multiple
cancer types.
Working together, the companies will
develop Lynparza and Koselugo in
combination with other potential new medicines and as
monotherapies. The companies will develop Lynparza and Koselugo in
combination with their respective PD-L1 and PD-1 medicines
independently.
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 and Zoladex and the next-generation oral selective
oestrogen receptor degrader (SERD) and potential new medicine
camizestrant.
The PARP inhibitor, Lynparza, is an approved targeted treatment option for
early and metastatic breast cancer patients with an inherited BRCA
mutation. AstraZeneca with MSD continue to
research Lynparza in breast cancer patients with an inherited
BRCA mutation.
Building on the initial approvals of Enhertu, a HER2-directed antibody drug conjugate (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. Enhertu has received approval in the US in
previously treated HER2-low metastatic breast
cancer.
To bring much needed treatment options to patients with
triple-negative breast cancer, an aggressive form of breast cancer,
AstraZeneca is testing immunotherapy Imfinzi 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. Tutt ANJ, et al. Adjuvant Olaparib for Patients with BRCA1- or
BRCA2-Mutated Breast Cancer. N Engl J
Med. 2021;384:2394-2405.
2. International Agency for Research
on Cancer. Globocan 2020 - Breast. Available at https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf.
Accessed August 2022.
3. Ganjoho. Projected Cancer
Statistics. Available at https://ganjoho.jp/reg_stat/statistics/stat/short_pred_en.html.
Accessed August 2022.
4. Heer
E, et
al. Global burden and
trends in premenopausal and postmenopausal breast cancer: a
population-based study. Lancet
Glob Health.
2020;8(8):e1027-37.
5. Healthline. What Does It Mean to
Have HER2-Negative Breast Cancer? Available at https://www.healthline.com/health/breast-cancer/her2-negative#:~:text=Most%20breast%20cancers%20are%20HER2,t%20produce%20too%20much%20HER2.
Accessed August 2022.
6.
Winter
C, et
al.
Targeted sequencing of BRCA1 and BRCA2 across a large unselected
breast cancer cohort suggests that one-third of mutations are
somatic. Ann.
Oncol.
2016 Cancer.gov.
Early-stage breast cancer. Available
at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/early-stage-breast-cancer. Accessed
August 2022.
7. Cancer.gov. Early-stage breast
cancer. Available
at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/early-stage-breast-cancer. Accessed
August 2022.
8. Cancer Research UK. Breast
cancer stages, types and grades. Available at https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-types-grades/number-stages/stage-1.
Accessed August 2022.
9. Hattori
M, et
al.
A systematic literature review of prognostic factors in patients
with HR+/HER2− advanced breast cancer in
Japan. Jpn
J Clin Oncol.
2021;51(10):1498-508.
10. Hayashi
N, et
al.
Annual report of the Japanese breast cancer registry for
2017. Breast
Cancer.
2020;27(5):803-9.
11. O'Shaughnessy
J, et
al. Prevalence of germline BRCA
mutations in HER2-negative metastatic breast cancer: global results
from the real-world, observational BREAKOUT
study. Breast Cancer
Research.
2020;22(114).
12. Colleoni M, et al. Annual Hazard Rates of Recurrence for Breast
Cancer During 24 Years of Follow-Up: Results From the International
Breast Cancer Study Group Trials I to V. J Clin
Oncol. 2016;34(9):927-935.
13. Yersal O and Barutca S. Biological
subtypes of breast cancer: Prognostic and therapeutic
implications. World J Clin
Oncol. 2014;5(3):412-424.
14. Rivenbark AG, et al. Molecular and Cellular Heterogeneity in
Breast Cancer: Challenges for Personalized
Medicine. Am J
Pathol. 2013;183:1113-1124.
15. ClinicalTrials.gov. Olaparib as Adjuvant
Treatment in Patients with Germline BRCA Mutated High Risk HER2
Negative Primary Breast Cancer (OlympiA). Available
at https://clinicaltrials.gov/ct2/show/NCT02032823.
Accessed August 2022.
16. Roy R, et al. BRCA1 and BRCA2: different roles in a common
pathway of genome protection. Nat Rev
Cancer. 2016;12(1):68-78.
17. Wu
J, et
al. The role of BRCA1 in
DNA damage response. Protein
Cell. 2010;1(2):117-123.
18. Gorodetska I, et al. BRCA
Genes: The Role in Genome Stability, Cancer Stemness and Therapy
Resistance. Journal of
Cancer. 2019;10:2109-2127.
19. Li H, et al. PARP inhibitor resistance: the underlying
mechanisms and clinical implications. Molecular
Cancer. 2020;19:1-16.
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 August 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|