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 December 2020
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza approved in Japan for the treatment of advanced ovarian,
prostate and pancreatic cancers
29 December 2020 07:00 GMT
Lynparza approved in Japan for the treatment of
advanced ovarian, prostate and pancreatic
cancers
Approvals based on the PAOLA-1, PROfound and POLO Phase III
trials
AstraZeneca and MSD's Lynparza (olaparib) has been approved in Japan for
the treatment of advanced ovarian, prostate and pancreatic
cancers.
The three approvals authorise Lynparza for: maintenance treatment after 1st-line
chemotherapy containing bevacizumab (genetical recombination) for
patients with homologous recombination repair deficient (HRD)
ovarian cancer; the treatment of patients with BRCA gene-mutated
(BRCAm) castrate-resistant prostate cancer with distant metastasis
(mCRPC); and as maintenance treatment after platinum-based
chemotherapy for patients with BRCAm curatively unresectable
pancreas cancer.
The concurrent approvals by the Japanese Ministry of Health,
Labour, and Welfare are based on positive results from
the PAOLA-1, PROfound and POLO Phase
III trials, which each were published in The New England Journal of
Medicine.
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "These three approvals allow patients in Japan to be treated
with Lynparza, a targeted treatment personalised to their
specific biomarkers. They further underline the critical importance
of biomarker testing at diagnosis, which helps physicians determine
a course of treatment tailored to individual patients to
substantially delay disease progression."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "For patients in Japan diagnosed with each of these types of
cancer there are very few treatment options. Approvals for
treatments such as Lynparza, the first PARP inhibitor to be approved in these
specific types of metastatic castration-resistant prostate cancer
and metastatic pancreatic cancer in Japan, enable us to advance
this evolving era of personalised medicine and change how these
cancers are treated."
Lynparza in ovarian
cancer
The approval as 1st-line maintenance treatment with bevacizumab for
patients with HRD-positive advanced ovarian cancer is based on a
biomarker subgroup analysis of the PAOLA-1 Phase III trial which
showed Lynparza, in combination with bevacizumab maintenance
treatment, demonstrated a substantial progression-free survival
(PFS) improvement versus bevacizumab alone, for patients with
HRD-positive advanced ovarian cancer.
In 2020, nearly 11,000 women in Japan were diagnosed with ovarian
cancer, with more than 5,000 women dying of the
disease.1 One
in two women with advanced ovarian cancer has an HRD-positive
tumour.2,3
Lynparza in prostate cancer
The approval for the treatment of BRCAm mCRPC is 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 Japan in advanced prostate cancer.
Prostate cancer is the third most common type of cancer in Japan
and in 2020, accounted for over 100,000 new
cases.1 With
limited treatment options, the average survival for men with mCRPC
is only 9-13 months.8 Approximately
12% of men with mCRPC have a BRCA mutation,5 a
subgroup of patients with a particularly poor
prognosis.
Lynparza in pancreatic
cancer
The approval for BRCAm metastatic pancreatic cancer is based on the
results of the POLO Phase III trial which
showed Lynparza demonstrated a statistically significant and
clinically meaningful improvement in PFS versus placebo in patients
with germline BRCAm metastatic pancreatic
cancer. Lynparza is the first and only PARP inhibitor
approved in this disease.
Pancreatic cancer has one of the lowest survival rates of the most
common cancers and in Japan was responsible for almost 40,000
deaths in 2020 - the fourth most common cause of cancer
death.1,5 Japan
has the third-highest rate of pancreatic cancer in the world with
44,000 new cases diagnosed in 2020.1,6 Approximately
5-7% of patients with metastatic pancreatic cancer have a germline
BRCA mutation.7
AstraZeneca and MSD are exploring additional trials in advanced
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. AstraZeneca is
exploring additional trials in advanced ovarian cancer, including
the DUO-O Phase III trial testing Imfinzi (durvalumab) in combination with
chemotherapy and bevacizumab, followed by maintenance treatment
with Imfinzi, bevacizumab, and Lynparza in newly diagnosed advanced ovarian cancer
patients.
PAOLA-1
PAOLA-1 is a double-blinded Phase III trial testing the efficacy
and safety of Lynparza added to standard-of-care bevacizumab
versus bevacizumab alone, as a 1st-line maintenance treatment for
newly diagnosed advanced FIGO Stage III-IV high-grade serous or
endometroid ovarian, fallopian tube, or peritoneal cancer patients
who had a complete or partial response to 1st-line treatment with
platinum-based chemotherapy and bevacizumab. AstraZeneca and
MSD announced in August
2019 that the trial met
its primary endpoint of PFS in the overall trial
population.
The PAOLA-1 Phase III trial showed that Lynparza, in combination with bevacizumab maintenance
treatment, reduced the risk of disease progression or death by 67%
(based on a hazard ratio [HR] of 0.33, 95% confidence interval [CI]
0.25-0.45). The addition of Lynparza improved PFS to a median of 37.2 months
versus 17.7 with bevacizumab alone in patients with HRD-positive
advanced ovarian cancer.
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 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 homologous recombination repair (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.
The subgroup analysis from the PROfound Phase III trial
showed Lynparza reduced the risk of disease progression or
death by 78% (based on a HR of 0.22, 95% 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.
POLO
POLO is a randomised, double-blinded, placebo-controlled,
multi-centre Phase III trial of Lynparza tablets (300mg twice daily) as maintenance
monotherapy versus placebo. The trial randomised 154 patients with
germline BRCAm metastatic pancreatic cancer whose disease had not
progressed on 1st-line platinum-based chemotherapy. Patients were
randomised (3:2) to receive Lynparza or placebo until disease progression. The
primary endpoint was PFS and key secondary endpoints included OS,
time to second disease progression, overall response rate and
health-related quality of life.
Data from the Phase III POLO trial showed Lynparza nearly doubled the time patients with
germline BRCAm metastatic pancreatic cancer lived without disease
progression or death to a median of 7.4 months versus 3.8 on
placebo and reduced the risk of disease progression or death by 47%
(based on a HR of 0.53, 95% CI 0.35-0.82;
p=0.004).
BRCA
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 are
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.8-11
HRD
HRD, which defines a subgroup of ovarian cancer, encompasses a wide
range of genetic abnormalities, including BRCA mutations and
beyond. As with BRCA gene mutations, HRD interferes with normal
cell DNA repair mechanisms and confers sensitivity to PARP
inhibitors including Lynparza.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 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 and EU 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 BRCA-mutated, 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
metastatic castration-resistant prostate cancer (BRCAm and other
HRR gene mutations) and in the EU 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, 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 six scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage
Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies
- 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.
The World Health Organization.
IARC. Globocan. (2020). Japan Factsheet. Available
at: https://gco.iarc.fr/today/data/factsheets/populations/392-japan-fact-sheets.pdf [Accessed
December 2020].
2.
Moschetta et al. (2016). BRCA somatic mutations
and epigenetic BRCA modifications in serous ovarian
cancer. Annals of
Oncology, 27(8),
pp.1449-1455.
3.
Bonadio et al. (2018). Homologous recombination
deficiency in ovarian cancer: a review of its epidemiology and
management. Clinics, 73(Suppl 1): e450s.
4.
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.
5.
Rawla
et al. (2019). Epidemiology of Pancreatic Cancer: Global Trends,
Etiology and Risk Factors. World Journal of Oncology, 10(1),
pp.10-27.
6.
The World Health Organization.
IARC. Globocan. (2020). Estimated age-standardized incidence rates
(World) in 2020, pancreas, both sexes, all ages.
Available here [Accessed
December 2020].
7.
Golan
et al. (2020). Geographic and Ethnic Heterogeneity of Germline
BRCA1 or BRCA2 Mutation Prevalence Among Patients With Metastatic
Pancreatic Cancer Screened for Entry Into the POLO Trial. Journal
of Clinical Oncology 2020; 38(13): 1442-1454.
8.
Kirby,
M. (2011). Characterising the castration-resistant prostate cancer
population: a systematic review. International Journal of Clinical
Practice, 65(11), pp.1180-1192.
9.
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.
10.
Wu J, et al. (2010) The role of BRCA1 in DNA
damage response. Protein
Cell.
2010;1(2):117-123.
11.
Gorodetska I, et al. (2019). BRCA Genes: The Role
in Genome Stability, Cancer Stemness and Therapy
Resistance. J Cancer. 2019;10(9):2109-2127.
12.
Moore, K. (2018). Maintenance Olaparib in Patients
with Newly Diagnosed Advanced Ovarian
Cancer. New England Journal of
Medicine, 379(26),
pp.2495-2505.
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:
29 December
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|