a9237c
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 June 2021
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 China for prostate cancer
24 June
2021 07:00 BST
Lynparza approved in China for the treatment of BRCA-
mutated metastatic castration-resistant prostate
cancer
Only PARP inhibitor to improve overall survival versus
new hormonal treatments in advanced prostate cancer
First PARP inhibitor approved in China in advanced prostate
cancer
AstraZeneca
and MSD's Lynparza
(olaparib) has been granted conditional approval in China to treat adult
patients with germline or somatic BRCA-mutated metastatic
castration-resistant prostate cancer (mCRPC) who have progressed
following treatment that included a new hormonal agent
(abiraterone, enzalutamide).
In China, prostate cancer is the
sixth most prevalent cancer in men, with approximately 115,000 new
patients diagnosed each year and about 7% have germline BRCA
mutations.1,2 Prostate cancer
patients with these mutations are more likely to have poorer
outcomes than those without the mutations.3 Around 70% of
prostate cancer patients in China have advanced disease at the time
of diagnosis, and for those with mCRPC, the median survival is less
than two years.4,5
The
approval by China's National Medical Products Administration was
based on a subgroup analysis of the PROfound Phase III trial, which
showed that Lynparza
demonstrated a substantial improvement in radiographic
progression-free survival (rPFS) and overall survival (OS) versus
abiraterone or enzalutamide in men with BRCA1/2 mutations.
Continued approval is contingent upon verification and description
of clinical benefit in a planned bridging trial with Chinese
patients.
Dave
Fredrickson, Executive Vice President, Oncology Business Unit,
said: "This approval begins a new era of precision medicine for
patients in China with advanced prostate cancer who have
historically had a poor prognosis and few treatment options.
Lynparza more than tripled
radiographic progression-free survival in the PROfound trial and is
the only PARP inhibitor to show an overall survival benefit
compared to treatment with new hormonal agents for men with
BRCA-mutated metastatic castration-resistant prostate
cancer."
Roy
Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "The approval underscores the critical importance of BRCA
testing in men with prostate cancer. We are proud to provide a new
personalised treatment option for men with this devastating disease
in China, and we will continue to collaborate with the Chinese
government and healthcare organisations to bring Lynparza to patients who need
it."
The
subgroup analysis from the PROfound Phase III trial showed
Lynparza reduced the risk
of disease progression or death by 78% (based on a hazard ratio
[HR] of 0.22, 95% confidence interval [CI] 0.15-0.32; nominal
p<0.0001) and improved rPFS to a median of 9.8 months versus 3.0
with abiraterone or enzalutamide in men with mCRPC with BRCA1/2
mutations. In addition, Lynparza reduced the risk of death by
37% (HR of 0.63, 95% CI 0.42-0.95) with median OS of 20.1 months
versus 14.4 with abiraterone or enzalutamide.
The
primary
results and OS results from
the PROfound Phase III trial were published in The New England Journal of
Medicine.
Lynparza is approved in the US to treat men
with homologous recombination repair gene-mutated (HRRm) mCRPC and
in the EU,
Japan
and several other countries for BRCA-mutated mCRPC patients based
on the PROfound Phase III trial. In addition, regulatory reviews
are ongoing in other countries around the world.
AstraZeneca
and MSD are testing Lynparza in additional trials in
metastatic prostate cancer, including the ongoing PROpel Phase III
trial of Lynparza as a
1st-line treatment for patients with mCRPC in combination with
abiraterone versus abiraterone alone. Results are anticipated in
the second half of 2021.
Metastatic castration-resistant prostate cancer
Prostate
cancer is associated with a significant mortality rate.6 Prostate cancer is
often driven by male sex hormones called androgens, including
testosterone.7 In patients with
mCRPC, prostate cancer grows and spreads to other parts of the body
despite the use of androgen-deprivation therapy to block the action
of male sex hormones.7 Approximately 10-20%
of men with advanced prostate cancer will develop CRPC within five
years, and at least 84% of these men will have metastases at the
time of CRPC diagnosis.8 Of men with no
metastases at CRPC diagnosis, 33% are likely to develop metastases
within two years.8 Despite advances in
treatment for men with mCRPC, five-year survival is low and
extending survival remains a key treatment goal.8
PROfound
PROfound
is a prospective, multicentre, randomised, open-label, Phase III
trial testing the efficacy and safety of Lynparza versus abiraterone or
enzalutamide in patients with mCRPC who have progressed on prior
treatment that included new hormonal agents (abiraterone or
enzalutamide) and have a qualifying tumour mutation in BRCA1/2, ATM
or one of 12 other genes involved in the HRRm pathway.
The
trial was designed to analyse patients with HRR gene mutations in
two cohorts: the primary endpoint was rPFS in those with mutations
in BRCA1/2 or ATM genes, and then, if Lynparza showed clinical benefit, a
formal analysis was performed of the overall trial population of
patients with HRR gene mutations (BRCA1/2, ATM and 12 other HRR
gene mutations). AstraZeneca and MSD announced in August
2019 that the trial met its primary endpoint of
rPFS.
BRCA1 and BRCA2
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. 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.9-12
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 HRR, such as mutations in
BRCA1 and/or BRCA2. Inhibition of PARP 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 being tested in a range of PARP-dependent tumour types with
defects and dependencies in the DDR pathway.
Lynparza is currently approved in several countries,
including those in the EU, for the maintenance treatment of
platinum-sensitive relapsed ovarian cancer. It is approved in the
US, the EU, Japan, China, and several other countries as 1st-line
maintenance treatment of BRCA-mutated (BRCAm) advanced ovarian
cancer following response to platinum-based chemotherapy. It is
also approved in the US, the EU, and Japan as 1st-line maintenance
treatment with bevacizumab for patients with HRD-positive advanced
ovarian cancer (BRCAm and/or genomic instability). In addition,
Lynparza is approved in the
US, Japan, and several other countries for germline BRCAm,
HER2-negative, metastatic breast cancer, previously treated with
chemotherapy; in the EU, this includes locally advanced breast
cancer. It is also approved in the US, the EU, Japan, and several
other countries to treat germline BRCAm metastatic pancreatic
cancer. In addition, Lynparza is approved in the US for HRR
gene-mutated mCRPC (BRCAm and other HRR gene mutations) and in the
EU and Japan for BRCAm metastatic castration-resistant prostate
cancer. Regulatory reviews are underway in several countries for
ovarian, breast, pancreatic and prostate cancers.
Lynparza, which is being jointly developed and
commercialised by AstraZeneca and MSD, has been used to treat over
40,000 patients worldwide. Lynparza has the broadest and most
advanced clinical trial development programme of any PARP
inhibitor. AstraZeneca and MSD are working together to understand
how it may affect multiple PARP-dependent tumours as a monotherapy
and in combination across multiple cancer types. Lynparza 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. Independently, the companies will develop
Lynparza
and
Koselugo
in
combination with their respective PD-L1 and PD-1
medicines.
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 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.
Gco.iarc.fr. Cancer
today - Estimated number of new cases in 2020, Asia, worldwide,
China, males, all ages. Available at: https://gco.iarc.fr/today/online-analysis-table
Accessed June 2021.
2.
Wei, Y.,
et al. Germline DNA Repair
Gene Mutation Landscape in Chinese Prostate Cancer Patients.
European
Urology,2019,76(3), pp.280-283.
3.
Messina, C.,
et al. BRCA Mutations in
Prostate Cancer: Prognostic and Predictive Implications.
Journal of Oncology, 2020,
pp.1-7.
4.
National Health
Commission of PRC, Chinese guidelines for diagnosis and treatment
of prostate cancer 2018 (English version). Chinese Journal of Cancer Research,
2019,31(1), pp.67-83.
5.
Zhu, Y.,
et al. Chinese Expert
Consensus on the Diagnosis and Treatment of Castration-Resistant
Prostate Cancer (2019 update). Cancer Manag Res. 2020; 12:
2127-2140.
6.
Bray, et al. Global cancer statistics 2018:
GLOBOCAN estimates of incidence and mortality worldwide for 36
cancers in 185 countries. CA: A Cancer Journal for Clinicians,
2018,68(6), pp.394-424.
7.
de Bono,
et al. Olaparib for
Metastatic Castration-Resistant Prostate Cancer. New England Journal of Medicine,
2020,382,pp.2091-102.
8.
Cancer.Net.
Treatment of metastatic castration-resistant prostate cancer.
Available at: https://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer.
Accessed June 2021.
9.
Kirby, M. (2011).
Characterising the castration-resistant prostate cancer population:
a systematic review. International Journal of Clinical Practice,
65(11), pp.1180-1192.
10.
Roy R, et al. (2012). BRCA1 and BRCA2:
different roles in a common pathway of genome protection. Nat Rev
Cancer. 2011;12(1):68-78. Published 2011 Dec 23.
doi:10.1038/nrc3181.
11.
Wu J, et al. (2010) The role of BRCA1 in DNA
damage response. Protein Cell. 2010;1(2):117-123.
12.
Gorodetska I, et
al. (2019). BRCA Genes: The Role in Genome Stability, Cancer
Stemness and Therapy Resistance. J Cancer.
2019;10(9):2109-2127.
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:
24 June
2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|