a7693k
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 April 2020
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza demonstrated
overall survival benefit in Phase III PROfound trial
for BRCA1/2 or ATM-mutated metastatic castration-resistant prostate
cancer
24 April 2020 07:00 BST
Lynparza demonstrated overall survival benefit in
Phase III PROfound trial
for BRCA1/2 or ATM-mutated metastatic castration-resistant prostate
cancer
Only PARP inhibitor to improve overall survival vs. new hormonal
agent treatments for this advanced prostate cancer population with
high unmet needs
AstraZeneca and MSD Inc., Kenilworth, N.J., US
(MSD: known as Merck & Co., Inc. inside the US and Canada)
today announced further positive results from the Phase III
PROfound trial of Lynparza (olaparib) in men with metastatic
castration-resistant prostate cancer (mCRPC) who have a homologous
recombination repair gene mutation (HRRm) and have progressed on
prior treatment with new hormonal agent (NHA) treatments (e.g.
enzalutamide and abiraterone).
Results from the trial showed a statistically
significant and clinically meaningful improvement in the key
secondary endpoint of overall survival (OS)
with Lynparza versus enzalutamide or abiraterone in men
with mCRPC selected for BRCA1/2 or ATM gene mutations, a
subpopulation of HRR gene mutations.
The Phase III PROfound trial had met its
primary endpoint in August
2019, showing
significantly improved radiographic progression-free survival
(rPFS) in men with mutations in BRCA1/2 or ATM genes, and had met a
key secondary endpoint of rPFS in the overall HRRm
population.
José Baselga, Executive Vice President,
Oncology R&D, said: "Overall survival in metastatic
castration-resistant prostate cancer has remained extremely
challenging to achieve. We are thrilled by these results
for Lynparza and we are working with regulatory
authorities to bring this medicine to patients as soon as
possible."
Roy Baynes, Senior Vice President and Head of
Global Clinical Development, Chief Medical Officer, MSD Research
Laboratories, said: "Lynparza has demonstrated significant clinical
benefit across key endpoints in PROfound, including overall
survival for patients with BRCA or ATM mutations, and this
reinforces its potential to change the treatment standard for
patients with metastatic castration-resistant prostate cancer.
These data further support MSD and AstraZeneca's commitment to
uncovering the ways in which Lynparza can help patients impacted by
cancer."
The safety and tolerability profile of Lynparza was generally consistent with previous
trials. The data will be presented at a forthcoming medical
meeting.
Lynparza was granted
Priority Review in the US for patients with HRRm mCRPC
in January
2020, with regulatory reviews
ongoing in the EU and other jurisdictions. AstraZeneca and MSD are
exploring additional trials in prostate cancer including the
ongoing Phase III PROpel trial, with first data expected in 2021,
testing Lynparza as a 1st-line medicine for patients with
mCRPC in combination with abiraterone acetate versus abiraterone
acetate alone.
Metastatic castration-resistant prostate cancer
Prostate cancer is the second-most common cancer in men, with an
estimated 1.3 million new cases diagnosed worldwide in 2018, and is
associated with a significant mortality rate.1 Development
of prostate cancer is often driven by male sex hormones called
androgens, including testosterone.2 In
patients with mCRPC, their 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.2 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.3 Of
men with no metastases at CRPC diagnosis, 33% are likely to develop
metastases within two years.3 Despite
advances in treatment for men with mCRPC, five-year survival is low
and extending survival remains a key goal for treating these
men.3
HRR gene mutations
HRR mutations occur in approximately 20-30% of patients with
mCRPC.4 HRR
genes allow for accurate repair of damaged DNA in normal
cells.5,6 HRR
deficiency (HRD) means the DNA damage cannot be repaired, and can
result in normal cell death.6 This
is different in cancer cells, where a mutation in HRR pathways
leads to abnormal cell growth and therefore
cancer.6 HRD
is a well-documented target for PARP inhibitors, such
as Lynparza. PARP inhibitors block a rescue DNA damage repair
mechanism by trapping PARP bound to DNA single-strand breaks which
leads to replication fork stalling causing their collapse and the
generation of DNA double-strand breaks, which in turn lead to
cancer cell death.6
PROfound
PROfound is a prospective, multicentre, randomised, open-label,
Phase III trial testing the efficacy and safety
of Lynparza versus enzalutamide or abiraterone in
patients with mCRPC who have progressed on prior treatment with NHA
treatments (abiraterone or enzalutamide) and have a qualifying
tumour mutation in BRCA1/2, ATM or one of 12 other genes involved
in the HRR pathway.
The trial was designed to analyse patients with HRRm genes 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 HRRm
genes (BRCA1/2, ATM, CDK12 and 11 other HRRm genes; a key secondary
endpoint).
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, 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 a number of 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
advanced ovarian cancer following response to platinum-based
chemotherapy. It is also approved in the US, Japan, and a number of
other countries for germline BRCA-mutated, HER2-negative,
metastatic breast cancer, previously treated with chemotherapy; in
the EU, this includes locally advanced breast
cancer. Lynparza is approved in the US and several other
countries for the treatment of germline BRCA-mutated metastatic
pancreatic cancer. Regulatory reviews are underway in several
jurisdictions 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 30,000 patients
worldwide. Lynparza has the broadest and most advanced clinical
trial development programme of any PARP inhibitor, and 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 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 has a deep-rooted heritage in oncology and offers a
quickly-growing portfolio of new medicines that has the potential to transform
patients' lives and the Company's future. With six new medicines
launched between 2014 and 2020, and a broad
pipeline of small molecules and biologics in development,
the Company is committed to advance oncology as a key growth driver
for AstraZeneca focused on lung, ovarian, breast and blood cancers.
In addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investment that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development
of personalised combinations, AstraZeneca has the vision to
redefine cancer treatment and, one day, eliminate cancer as a cause
of death.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, Cardiovascular, Renal and Metabolism, and Respiratory.
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. Bray et al. (2018). Global cancer
statistics 2018: GLOBOCAN estimates of incidence and mortality
worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for
Clinicians, 68(6),
pp.394-424.
2. Cancer.Net. (2019). Treatment of
metastatic castration-resistant prostate
cancer. www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer [Last
Accessed: November 2019].
3. Kirby, M., 2011. Characterising the
castration-resistant prostate cancer population: a systematic
review. International Journal of
Clinical Practice, 65(11),
pp.1180-1192.
4. Mateo, J, et al (2015). DNA-repair
defects and olaparib in metastatic prostate
cancer. New England Journal of
Medicine, 373(18), pp.1697 -
1708.
5. Li et al. (2008). Homologous
recombination in DNA repair and DNA damage
tolerance. Cell
Research, 18(1),
pp.99-113.
6. Ledermann et al. (2016). Homologous
recombination deficiency and ovarian
cancer. European Journal of
Cancer, 60,
pp.49-58.
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 April 2020
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By: /s/
Adrian Kemp
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|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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