a5904e
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
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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
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|