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 November 2020
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 the
EU for the treatment of BRCA-
mutated metastatic castration-resistant prostate cancer
5 November 2020 07:10 GMT
Lynparza approved in the EU for the treatment of
BRCA-
mutated metastatic castration-resistant prostate
cancer
Only PARP inhibitor to improve overall survival vs. new hormonal
agent treatments in BRCA-mutated metastatic castration-resistant
prostate cancer
AstraZeneca and MSD's Lynparza (olaparib) has been approved in the European
Union (EU) for patients with metastatic castration-resistant
prostate cancer (mCRPC) with breast cancer susceptibility gene 1/2
(BRCA1/2) mutations, a subpopulation of homologous recombination
repair (HRR) gene mutations.
Prostate cancer is the second-most common type of cancer in men,
with an estimated 1.3 million patients diagnosed worldwide in
2018.1 Approximately
12% of men with mCRPC have a BRCA mutation.2
The approval by the European Commission was based on a subgroup
analysis of the PROfound Phase III trial which
showed Lynparza demonstrated a substantial improvement in
radiographic progression-free survival (rPFS) and overall survival
(OS) versus enzalutamide or abiraterone in men with BRCA1/2
mutations.
Lynparza is the first and
only PARP inhibitor approved in the EU in biomarker-selected
advanced prostate cancer. It follows
the recommendation for
approval by the Committee
for Medicinal Products for Human Use of the European Medicines
Agency in September 2020.
Johann de Bono, one of the principal investigators of the PROfound
Phase III trial, Head of Drug Development at The Institute of
Cancer Research, London, and The Royal Marsden NHS Foundation
Trust, said: "This approval in the EU is a landmark moment that
begins a new era of precision medicine in prostate
cancer. Lynparza now provides a targeted treatment option at
a molecular level to patients with advanced prostate cancer who
have historically poor prognosis and few treatment
options."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "Lynparza more than tripled radiographic
progression-free survival and is the only PARP inhibitor to show an
overall survival benefit versus certain new hormonal agents for men
with BRCA-mutated metastatic castration-resistant prostate cancer.
This approval means BRCA testing should now become a critical
step in the diagnosis and determination of treatment for men with
advanced prostate cancer in the EU."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "The PROfound Phase III trial
showed Lynparza provided a clinical benefit for men living
with BRCA1/2-mutated metastatic castration-resistant prostate
cancer, offering an important option to improve overall survival
for these patients in the EU. MSD, along with our collaborator
AstraZeneca, looks forward to making this targeted treatment
available for patients across the EU as quickly as
possible."
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 enzalutamide or abiraterone in men with mCRPC with
BRCA1/2 mutations. Lynparza reduced the risk of death by 37% (based on a
HR of 0.63, 95% CI 0.42-0.95) with median OS of 20.1 months versus
14.4 with enzalutamide or abiraterone.
The primary
results and overall
survival results from the
PROfound Phase III trial were published in The New England Journal of
Medicine earlier this
year.
The full EU approved indication for Lynparza is for the treatment of adult patients with
mCRPC and BRCA1/2 mutations (germline and/or somatic) who have
progressed following prior therapy that included a new hormonal
agent.
Lynparza was approved
in the US for men with HRR gene-mutated mCRPC
in May
2020 based on the PROfound
Phase III trial. Regulatory reviews are ongoing in other countries
around the world.
AstraZeneca and MSD are exploring additional trials in metastatic
prostate cancer including the ongoing PROpel Phase III trial
testing Lynparza as a 1st-line treatment for patients with
mCRPC in combination with abiraterone versus abiraterone alone.
Data are anticipated in the second half of
2021.
Metastatic castration-resistant prostate cancer
Prostate cancer is associated with a significant mortality
rate.1 Prostate
cancer is often driven by male sex hormones called androgens,
including testosterone. 3 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.3 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. 4 Of
men with no metastases at CRPC diagnosis, 33% are likely to develop
metastases within two years. 4 Despite
advances in treatment for men with mCRPC, five-year survival is low
and extending survival remains a key treatment
goal.4
BRCA mutations
BRCA1 and BRCA2 are human genes that produce proteins responsible
for repairing damaged DNA and play an important role in 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.5-8
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 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, CDK12 and 11 other HRR gene
mutations). AstraZeneca and MSD announced in August
2019 that the trial met
its primary endpoint of rPFS.
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 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 BRCAm advanced
ovarian cancer following response to platinum-based chemotherapy.
It is also approved in the US as a 1st-line maintenance treatment
with bevacizumab for patients with HRD-positive advanced ovarian
cancer (BRCAm and/or genomic instability). Lynparza is approved in the US, Japan, and a number
of 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 and several other countries for the treatment of
germline BRCAm metastatic pancreatic
cancer. Lynparza is approved in the US for HRR gene-mutated
mCRPC (BRCAm and other HRR gene mutations). 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 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 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 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 seven 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.
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/Nasdaq: 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 & 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. 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. Abida et al. (2020). Rucaparib in Men With Metastatic
Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2
Gene Alteration. Journal of Clinical
Oncology,
38.
3. de Bono et al. (2020) Olaparib for Metastatic
Castration-Resistant Prostate Cancer. New England Journal of
Medicine, 382,
pp.2091-102.
4. Cancer.Net. (2014). 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 September 2020]
5. Kirby, M. (2011). Characterising the castration-resistant
prostate cancer population: a systematic review. International
Journal of Clinical Practice, 65(11), pp.1180-1192.
6. Wu J, et al. (2010) The role of BRCA1 in DNA damage response.
Protein Cell. 2010;1(2):117-123.
7. 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.
8. 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:
05 November
2020
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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