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
2019
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
as a 1st-line maintenance therapy in BRCA-mutated advanced ovarian
cancer
05
December 2019 07:00 GMT
Lynparza approved in China as a 1st-line
maintenance
therapy in BRCA-mutated advanced ovarian cancer
AstraZeneca and MSD's Lynparza reduced the risk of disease
progression
or death by 70% in BRCAm advanced ovarian cancer after response
to 1st-
line platinum-based chemotherapy
Only PARP inhibitor approved in this setting in China
AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck
& Co., Inc. inside the US and Canada) today announced that the
companies have received marketing authorisation from China's
National Medical Products Administration
(NMPA) for Lynparza (olaparib) as a 1st-line maintenance
treatment of adult patients with newly diagnosed advanced germline
or somatic BRCA mutated (gBRCAm or sBRCAm) epithelial ovarian,
fallopian tube or primary peritoneal cancer who are in complete or
partial response to 1st-line platinum-based
chemotherapy.
The approval in China is based on the results from the Phase III
SOLO-1 trial, which were published in The
New England Journal of Medicine. Results showed that Lynparza significantly reduced the risk of disease
progression or death by 70% (equal to a hazard ratio of 0.30) vs.
placebo in women with BRCAm advanced ovarian cancer following
response to platinum-based chemotherapy. Of those women
receiving Lynparza, 60% remained progression-free at three years vs.
27% of women receiving placebo.
For newly diagnosed advanced ovarian cancer patients, the primary
aim of treatment is to delay progression of the disease for as long
as possible, with the intent of achieving complete remission or
cure. Of women diagnosed with
ovarian cancer, 15% have a germline (inherited) mutation and 7%
have a somatic (acquired) mutation in their BRCA1/2
genes.
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "This approval marks a new era for women with BRCA-mutated
advanced ovarian cancer in China, where the prevalence of BRCA
mutations in advanced disease is higher than the international
average. Currently, 70% of women relapse within three years of
initial treatment, representing the highest reoccurrence rate among
gynaecological cancers worldwide. The progression-free survival
benefit of Lynparza observed in SOLO-1 is a significant step
towards helping these women achieve long-term
remission."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "Today's approval of Lynparza reinforces the importance of patients
knowing their BRCA mutation status at diagnosis. We are proud to
provide a new option for the treatment of this devastating disease
in China, and we will continue to collaborate with the Chinese
government and healthcare organisations to
provide Lynparza to patients who need it as quickly as
possible."
Lynparza is the first PARP
inhibitor approved in China for 1st-line maintenance in BRCAm
advanced ovarian cancer. AstraZeneca and MSD are exploring additional
trials in ovarian cancer and recently announced positive
results from the Phase III
PAOLA-1 trial, which tested Lynparza in combination with bevacizumab as a
1st-line maintenance treatment for women with newly-diagnosed
advanced ovarian cancer, regardless of their biomarker status or
surgical outcome.
About SOLO-1
SOLO-1 was a Phase III, randomised, double-blinded,
placebo-controlled, multi-centre trial to evaluate the efficacy and
safety of Lynparza tablets (300mg twice daily) as a maintenance
monotherapy compared with placebo in patients with BRCAm advanced
ovarian cancer following 1st-line platinum-based chemotherapy. The
trial randomised 391 patients with a deleterious or suspected
deleterious germline or somatic BRCA1 or BRCA2 mutation who were in
clinical complete or partial response following platinum-based
chemotherapy.
Patients were randomised (2:1) to receive Lynparza or placebo for up to two years or until
disease progression. Patients who had a partial response at two
years were permitted to stay on therapy at the investigator's
discretion. The primary endpoint was progression-free survival
(PFS) and key secondary endpoints included time to second disease
progression or death, time to first subsequent treatment and
overall survival.
Summary of PFSi,ii
|
Lynparza (n=260)
|
Placebo
(n=131)
|
Number
of patients with event (%)iii
|
102
(39)
|
96
(73)
|
Median
PFS (in months)
|
Not
reached
|
13.8
|
Hazard
ratio (95% CI)
|
0.30
(0.23-0.41)
|
P-value
|
p<0.001
|
i Investigator-assessed.
ii Median (interquartile range) duration of follow-up 40.7 months
(34.9-42.9) for Lynparza and
41.2 months (32.2-41.6) for placebo.
iii Analysis was done at 50.6% maturity.
The SOLO-1 safety profile was in line with that observed in prior
clinical trials, and with no detriment to quality of life. The most
common adverse events (AEs) ≥ 20% were nausea (77%), fatigue
(63%), vomiting (40%), anaemia (39%) and diarrhoea (34%). The most
common ≥ Grade 3 AEs were anaemia (22%) and neutropenia (9%).
Some 71% of patients on Lynparza remained on the recommended starting dose.
Additionally, 88% of patients on Lynparza continued treatment without an AE-related
discontinuation.
The data were presented on 21 October 2018, at the Presidential
Symposium of the European Society of Medical Oncology (ESMO) 2018
Congress in Munich, Germany.
About ovarian cancer
Ovarian cancer is the eighth most common cause of death from cancer
in women worldwide. In 2018, there were nearly 300,000 new cases
diagnosed and around 185,000 deaths.1 China
has the highest prevalence of ovarian cancer globally, with more
than 52,000 new cases diagnosed in 2018 and approximately 30,886
deaths.1,2 Most
women are diagnosed with advanced (Stage III or IV) ovarian cancer
and have a five-year survival rate of approximately
30%.3 Of
women diagnosed with ovarian cancer, 15% have a germline mutation
and 7% have a somatic mutation in their BRCA1/2
genes.4,5 For
newly-diagnosed advanced ovarian cancer, the primary aim of
treatment is to delay progression of the disease for as long as
possible with the intent of achieving complete remission or
cure.6,7,8,9
About BRCA mutations
BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) 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 such as
breast and ovarian cancer.10
About 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
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 65 countries, including those in the EU, for the
maintenance treatment of platinum-sensitive relapsed ovarian
cancer, regardless of BRCA status. It is approved in the US, the
EU, Japan 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 44
countries, including the US and Japan, for germline BRCA-mutated,
HER2-negative, metastatic breast cancer, previously treated with
chemotherapy; in the EU, this includes locally advanced breast
cancer. Regulatory reviews are underway in other jurisdictions for
ovarian, breast and pancreatic cancers.
Lynparza, which is being
jointly developed and commercialised by AstraZeneca and MSD, is
approved for advanced ovarian cancer and metastatic breast cancer
and has been used in over 25,000 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.
About the AstraZeneca and MSD strategic oncology
collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth,
NJ, US, known as MSD outside the United States and Canada,
announced a global strategic oncology collaboration to co-develop
and co-commercialise Lynparza,
the world's first PARP inhibitor, and potential new medicine
selumetinib, a MEK inhibitor, for multiple cancer types. Working
together, the companies will develop Lynparza and
selumetinib in combination with other potential new medicines and
as monotherapies. Independently, the companies will
develop Lynparza and
selumetinib in combination with their respective PD-L1 and PD-1
medicines.
About 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 at
least six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in development, we
are committed to advance Oncology as one of AstraZeneca's four
Growth Platforms focused on lung, ovarian, breast and blood
cancers. In addition to our core capabilities, we actively pursue
innovative partnerships and investments that accelerate the
delivery of our strategy, as illustrated by our 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.
About AstraZeneca
AstraZeneca 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. 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.
Media
Relations
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|
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Viña
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+44 203
749 5916
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Rob
Skelding
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Oncology
|
+44 203
749 5821
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Rebecca
Einhorn
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+1 301
518 4122
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Kent
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BioPharmaceuticals
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+44 203
749 5906
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Hursit
|
Other
|
+44
203 749 5762
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8 552 53 106
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Meixell
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+1 302
885 2677
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Relations
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Thomas
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References
1. Worldovariancancercoalition.org. (2019). THE WORLD OVARIAN
CANCER COALITION ATLAS. Available at: https://worldovariancancercoalition.org/wp-content/uploads/2018/10/THE-WORLD-OVARIAN-CANCER-COALITION-ATLAS-2018.pdf [Accessed
October 2019].
2. The World Health Organization. IARC. Globocan 2018. Available
at: http://gco.iarc.fr/ [Accessed
August 2019].
3. National Cancer Institute. (2019). Cancer Stat Facts: Ovarian
Cancer Available at: https://seer.cancer.gov/statfacts/html/ovary.html [Accessed
August 2019].
4. Neff, R., Senter, L. and Salani, R. (2017). BRCA mutation in
ovarian cancer: testing, implications and treatment considerations.
Therapeutic Advances in Medical Oncology, 9(8),
pp.519-531.
5. Bonadio, R., Fogace, R., Miranda, V. and Diz, M. (2018).
Homologous recombination deficiency in ovarian cancer: a review of
its epidemiology and management. Clinics, 73(Suppl 1).
6. Moore K et al. Maintenance Olaparib in Patients with Newly
Diagnosed Advanced Ovarian Cancer. resented at ESMO October 2018.
Available at
https://www.ncbi.nlm.nih.gov/pubmed/30345884.
7. Raja, F. A., Chopra, N. & Ledermann, J. A. 2012. Optimal
first-line treatment in ovarian cancer. Ann. Oncol. Off. J. Eur. Soc.
Med. Oncol. 23 Suppl 10,
x118-127.
8. NHS Choices, Ovarian Cancer Available
at: https://www.nhs.uk/conditions/ovarian-cancer/treatment/ [Accessed
August 2019].
9. Ledermann.et al. 2013. Newly diagnosed and relapsed epithelial
ovarian carcinoma: ESMO Clinical Practice for diagnosis, treatment
and follow-up. Annals of
Oncology, 24(suppl 6),
pp.vi24-vi32.
10. National Cancer Institute. (2018). BRCA Mutations: Cancer Risk
and Genetic Testing. Available at: https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet [Accessed
October 2019].
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 December
2019
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|