a9051u
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 EU for early breast cancer
4
August 2022 07:00 BST
Lynparza approved
in the EU as adjuvant treatment for patients
with
germline
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 the European Union (EU) as
monotherapy or in combination with endocrine therapy for the
adjuvant treatment of adult patients with germline BRCA1/2
mutations (gBRCAm), who have human epidermal growth factor receptor
2 (HER2)-negative high-risk early breast cancer previously treated
with neoadjuvant or adjuvant chemotherapy.
This
approval by the European Commission was based on results from the
OlympiA
Phase III trial published in The
New England Journal of Medicine in
June 2021 and follows the recommendation for
approval in the EU by the Committee for Medicinal Products
for Human Use of Lynparza
in this setting.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 (OS), reducing the risk of death by 32% versus
placebo (based on a 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 Approximately 90% of
all breast cancer patients worldwide are diagnosed with early
breast cancer and BRCA mutations are found in approximately 10% of
HER2-negative patients in Europe.3-5
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 in Europe for patients with an inherited form of
breast cancer. 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. Olaparib is the first PARP inhibitor to demonstrate
improved overall survival for high-risk early-stage breast cancer
patients with germline BRCA mutations and I am hopeful it will
become a new standard of care.”
Dave
Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said:
“With
this approval, Lynparza is
now the first and only PARP inhibitor available for patients with
germline BRCA-mutated HER2-negative early breast cancer in Europe.
We can now bring the benefits of Lynparza to this earlier setting to
help reduce the risk of life-threatening
recurrence.”
Dr
Eliav Barr, Senior Vice President, Head of Global Clinical
Development and Chief Medical Officer, MSD Research Laboratories,
said: “Today’s approval offers patients with germline
BRCA-mutated HER2-negative early-stage breast cancer a new,
much-needed treatment option. Lynparza as adjuvant treatment can
significantly reduce the risk of disease recurrence and death,
reinforcing the importance of conducting germline BRCA testing as
soon as possible after diagnosis.”
In
March 2022, Lynparza was
approved in the
US for the treatment of gBRCAm, HER2-negative high-risk early
breast cancer. 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
Financial considerations
Following
this approval for Lynparza
in the EU, AstraZeneca will receive a regulatory milestone payment
from MSD of $75m, anticipated to be booked as Collaboration Revenue
during the third quarter of 2022.
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.6,7 In the EU, breast
cancer alone accounts for approximately 29% of all cancers in women
with 1 in 7 women developing the disease in their lifetime. In
2020, breast cancer accounted for an estimated 350,000 new cases
and over 90,000 deaths.8 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.5,9
Breast
cancer is one of the most biologically diverse tumour types with
various factors fuelling its development and
progression.10 The discovery of
biomarkers in the development of breast cancer has greatly impacted
scientific understanding of the disease.11
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.12
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.9 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.13-16
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.
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.
Cardoso F,
et al. Locally recurrent or
metastatic breast cancer: ESMO Clinical Practice Guidelines for
diagnosis, treatment and follow-up. Ann. Oncol.
2012;23:vii11-9.
4.
Asselain B,
et al. Long-term outcomes
for neoadjuvant versus adjuvant chemotherapy in early breast
cancer: meta-analysis of individual patient data from ten
randomised trials. Lancet.
Oncol. 2018;19(1):27-39.
5.
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).
6.
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 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.
8.
European
Commission. Breast cancer burden in EU-27. Available at
https://ecis.jrc.ec.europa.eu/pdf/Breast_cancer_factsheet-Oct_2020.pdf.
Accessed August 2022.
9.
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.
10.
Yersal O and
Barutca S. Biological subtypes of breast cancer: Prognostic and
therapeutic implications. World J
Clin Oncol. 2014;5(3):412-424.
11.
Rivenbark AG,
et al. Molecular and
Cellular Heterogeneity in Breast Cancer: Challenges for
Personalized Medicine. Am J
Pathol. 2013;183:1113-1124.
12.
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.
13.
Roy R, et al. BRCA1 and BRCA2: different roles
in a common pathway of genome protection. Nat Rev Cancer.
2016;12(1):68-78.
14.
Wu J, et al. The role of BRCA1 in DNA damage
response. Protein Cell.
2010;1(2):117-123.
15.
Gorodetska I,
et al. BRCA Genes: The Role
in Genome Stability, Cancer Stemness and Therapy Resistance.
Journal of Cancer.
2019;10:2109-2127.
16.
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:
04 August
2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|