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 March 2022
Commission File
Number: 001-11960
AstraZeneca
PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge CB2
0AA
United
Kingdom
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AstraZeneca
PLC
INDEX
TO EXHIBITS
1.
Lynparza approved
in US for early breast cancer
14
March 2022 07:05 GMT
Lynparza approved in the
US 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
New data show Lynparza demonstrated overall survival benefit in
early breast cancer
AstraZeneca and MSD's Lynparza (olaparib) has been approved in the US for
the adjuvant treatment of patients with germline BRCA-mutated
(gBRCAm) HER2-negative high-risk early breast cancer who have
already been treated with chemotherapy either before or after
surgery.
The approval by the US Food and Drug
Administration (FDA) was based on results from the OlympiA Phase
III trial presented during the 2021 American Society of
Clinical Oncology Annual Meeting and published
in The
New England Journal of Medicine.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,
second cancers or death, by 42% versus placebo (based on a hazard
ratio [HR] of 0.58; 95% confidence interval [CI] 0.46-0.74;
p<0.0001).
New updated results from the OlympiA trial also
showed Lynparza demonstrated a statistically significant and
clinically meaningful improvement in the key secondary endpoint of
overall survival (OS), reducing the risk of death by 32% versus
placebo (based on a HR of 0.68; 95% CI 0.50-0.91; p=0.0091). The
safety and tolerability profile of Lynparza in this trial was in line with that observed
in prior clinical trials. The OS data will be presented at an
upcoming European Society for Medical Oncology virtual plenary on
16 March 2022.
Breast cancer is the most diagnosed cancer
worldwide with an estimated 2.3 million patients diagnosed in
2020.2 Almost
91% of all breast cancer patients in the US are diagnosed at an
early stage of disease and BRCA mutations are found in
approximately 5-10% of patients.3,4
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 of olaparib is
great news for patients with a specific inherited form of breast
cancer. Most breast cancers are identified in the early stages and
many patients will do very well, but for those with higher risk
disease at diagnosis, the risk of cancer returning can be
unacceptably high and new treatment options are needed. OlympiA has
shown that identifying a BRCA1/2 mutation in women with high risk
disease opens the additional option of eligibility for olaparib
treatment, which reduces the risk of recurrence and improves
survival for these breast cancer patients."
Dave Fredrickson, Executive Vice President,
Oncology Business Unit, AstraZeneca, said: "This important approval
gives early-stage breast cancer patients in the US with a germline
BRCA mutation a new targeted therapy option in the adjuvant setting
starting today. Lynparza reduces the risk of disease recurrence in
these high-risk patients and now new data confirm it also
significantly extends patients' lives versus placebo. These data
underline the importance of germline BRCA testing as soon as
possible after diagnosis to identify patients that may be eligible
for Lynparza."
Roy Baynes, Senior Vice President and Head of
Global Clinical Development, Chief Medical Officer, MSD Research
Laboratories, said: "For patients with germline BRCA-mutated,
HER2-negative high-risk early breast cancer, who often present with
more aggressive disease, today's approval is an important step
forward. Compared to placebo, Lynparza as adjuvant treatment offers these patients
the potential to live longer without their cancer recurring. We
thank the patients, caregivers and healthcare providers for their
participation in the OlympiA trial."
Lynparza is now indicated for the adjuvant treatment
of adult patients with deleterious or suspected deleterious gBRCAm
HER2-negative high-risk early breast cancer who have been treated
with neoadjuvant or adjuvant chemotherapy. Patients are to be
selected for treatment based on an FDA-approved companion
diagnostic test for Lynparza.
Lynparza is
approved in the US, EU, Japan and several 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 US, AstraZeneca will receive a
regulatory milestone payment from MSD of $175m, anticipated to be
booked as Collaboration Revenue by the Company during the first
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.5 In
the US, the 5-year survival rate is 99% for localised breast cancer
(only found in the breast area) and 86% for regional breast cancer
(cancer that has spread outside the breast to nearby structures or
lymph nodes).3
Despite advances 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
years6,
and patients with gBRCA mutations are more likely to be diagnosed
at a younger age than those without these
mutations.7
Breast cancer is one of the most biologically
diverse tumour types with various factors fuelling its development
and progression.8 The
discovery of biomarkers in the development of breast cancer has
greatly impacted scientific understanding of the
disease.9
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.10
The primary endpoint of the trial is iDFS defined
as time from randomisation to date of first locoregional or distant
recurrence or new cancer or death from any
cause.11
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.12
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 genetic alterations that can lead to
cancer and confer sensitivity
to PARP inhibitors including Lynparza.11-14
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 germline
BRCAm, HER2-negative metastatic breast cancer (in the EU this
includes locally advanced breast cancer); for germline BRCAm
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 first approval
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. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN
Estimates of Incidence and Mortality Worldwide for 36 Cancers in
185 Countries. CA: A Cancer Journal for
Clinicians.
2020;0:1-41.
3. American Cancer Society. Breast
Cancer Facts & Figures 2019-2020. Available
at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2019-2020.pdf.
Accessed January 2021.
4. Cancer.gov. Early-stage breast
cancer. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/early-stage-breast-cancer.
Accessed January 2021.
5. Union for International Cancer
Control. Early-stage breast cancer -2014 Review of Cancer Medicines
on the WHO List of Essential Medicines. Available
at https://www.who.int/selection_medicines/committees/expert/20/applications/EarlyStageBreast.pdf?ua=1.
Accessed January 2021.
6. 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 Mar 20;
34(9):927-935.
7. 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).
8. Yersal O, Barutca S. Biological
subtypes of breast cancer: Prognostic and therapeutic
implications. World J Clin
Oncol. 2014;5(3):412-424.
9. Rivenbark AG, et al. Molecular and Cellular Heterogeneity in
Breast Cancer: Challenges for Personalized
Medicine. Am J Pathol. 2013;183:1113-1124.
10. 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 January 2021.
11. Roy R, et al. BRCA1 and BRCA2: different roles in a common
pathway of genome protection. Nat Rev
Cancer. 2016;12(1):68-78.
12. Wu J, et al. The role of BRCA1 in DNA damage
response. Protein
Cell 2010;1(2):117-123.
13. Gorodetska
I, et
al. BRCA Genes: The Role
in Genome Stability, Cancer Stemness and Therapy
Resistance. Journal of
Cancer. 2019;10:2109-2127.
14. 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:
14 March 2022
|
|
By: /s/
Adrian Kemp
|
|
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Name:
Adrian Kemp
|
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Title:
Company Secretary
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