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FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
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the
Securities Exchange Act of 1934
For the
month of October
2018
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza shows 70%
reduction in PFS ovarian cancer
22 October
2018 07:00 BST
SOLO-1 Phase III trial
demonstrates Lynparza maintenance therapy cut risk of disease
progression or death by 70% in patients with newly-diagnosed,
advanced BRCA-mutated ovarian cancer
60% of patients receiving Lynparza remained progression-free at
three years compared to 27% on placebo following platinum-based
chemotherapy
Lynparza is the only PARP inhibitor to demonstrate an improvement
in progression-free survival as 1st-line maintenance treatment for
advanced ovarian cancer
AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck:
known as MSD outside the US and Canada) today announced detailed
results from the Phase III SOLO-1 trial
testing Lynparza (olaparib) tablets as a maintenance
treatment for patients with newly-diagnosed,
advanced BRCA-mutated (BRCAm) ovarian cancer who were in complete or partial
response following 1st-line standard platinum-based chemotherapy.
Results of the trial confirm the statistically-significant and
clinically-meaningful improvement in progression-free survival
(PFS) for Lynparza compared to placebo, reducing the risk of
disease progression or death by 70% (HR 0.30 [95% CI 0.23-0.41],
p<0.001). At 41 months of follow-up, the median PFS for patients
treated with Lynparza was not reached compared to 13.8 months for
patients treated with placebo. Of those
receiving Lynparza, 60% remained progression-free at 36 months
compared to 27% of women in the placebo arm. The data were
presented at the Presidential Symposium of the ESMO 2018 Congress
(European Society for Medical Oncology) in Munich, Germany and
published simultaneously online in the New England Journal of
Medicine (NEJM).
Kaplan-Meier estimates of investigator-assessed PFS
Click on, or paste the following link into your web browser, to
view the associated PDF document.
http://www.rns-pdf.londonstockexchange.com/rns/6889E_1-2018-10-21.pdf
From the New England Journal of Medicine, Moore K, Colombo N,
Scambia G, et al. Maintenance olaparib in patients with newly
diagnosed advanced ovarian cancer. N Engl J Med. DOI:
10.1056/NEJMoa1810858. Copyright © 2018 Massachusetts Medical
Society. Reprinted with permission from Massachusetts Medical
Society.
Summary of PFS1,2
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Lynparza (n=260)
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Placebo
(n=130)
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Number
of patients with event (%)3
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102
(39)
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96
(73)
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Median
(in months)
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Not
reached
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13.8
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Hazard
ratio (95% CI)
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0.30
(0.23-0.41)
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P-value
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p<0.001
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1 Investigator-assessed
2 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
3 Analysis was done at
50.6% maturity
Sean Bohen, Executive Vice President, Global Medicines Development
and Chief Medical Officer, said: "There is currently a significant
unmet need in the treatment of advanced ovarian cancer because 70%
of women relapse within the first three years after their initial
treatment. The remarkable results of the SOLO-1 trial, which showed
that 60% of women with newly-diagnosed,
advanced BRCA-mutated ovarian cancer remained progression-free
at three years, highlight the potential of Lynparza as a maintenance therapy in the 1st-line
setting."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "Our collective goal in oncology research is to improve
long-term outcomes for people living with cancer. Based on the
SOLO-1 trial results, Lynparza is
the only PARP inhibitor to have demonstrated a significant and
clinically-meaningful improvement in reducing the risk of
progression for newly-diagnosed patients with
advanced BRCA-mutated
ovarian cancer following platinum-based chemotherapy. We are
working with regulatory authorities as quickly as possible to seek
approval of Lynparza for
these patients."
Kathleen Moore, Co-Principal Investigator of the SOLO-1 trial and
Associate Director for Clinical Research at the Stephenson Cancer
Center at the University of Oklahoma, Oklahoma City, US, said:
"Women with ovarian cancer are often diagnosed with advanced
disease, which unfortunately is associated with poor long-term
survival rates. The newly-diagnosed setting is our best opportunity
to achieve a sustained remission, since once a patient's ovarian
cancer recurs, it is typically incurable. The SOLO-1 results
demonstrate the potential of Lynparza maintenance therapy earlier in the treatment
pathway and reinforce the importance of identifying a
patient's BRCA mutation status at the time of diagnosis -
these results could change the way we treat women with
advanced BRCA-mutated ovarian cancer."
The SOLO-1 safety profile was in line with that observed in prior
clinical trials. The most common adverse events (AEs) ≥20%
were nausea (77%), fatigue/asthenia (63%), vomiting (40%), anaemia
(39%) and diarrhoea (34%). The most common ≥ grade 3 AEs were
anaemia (22%) and neutropenia (9%). Seventy-two percent of patients
on Lynparza remained on the recommended starting dose.
Additionally, 88% of patients on Lynparza continued treatment without an AE-related
discontinuation.
AstraZeneca and MSD are exploring additional trials in ovarian
cancer, including the ongoing GINECO/ENGOTov25 Phase III trial,
PAOLA-1. This trial is testing the effect
of Lynparza in combination with bevacizumab as a
maintenance treatment for patients with newly-diagnosed advanced
ovarian cancer, regardless of their BRCA status. Results are expected during the
second half of 2019.
Lynparza is currently approved in over 60 countries for
the treatment of platinum-sensitive relapsed ovarian
cancer regardless of BRCA status and in the US, Canada,
Japan and Australia for germline BRCA-mutated HER2-negative metastatic
breast cancer.
About SOLO-1
SOLO-1 is a Phase III randomised, double-blinded,
placebo-controlled, multicentre trial to evaluate the efficacy and
safety of Lynparza tablets (300 mg twice daily) as maintenance
monotherapy compared with placebo, in newly-diagnosed patients with
advanced BRCAm ovarian cancer following platinum-based
chemotherapy. The trial randomised 391 patients with a deleterious
or suspected deleterious 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 (at the investigator's discretion). The primary
endpoint was PFS and key secondary endpoints included time to
second disease progression or death, time to first subsequent
treatment and overall survival.
About Lynparza
Lynparza (olaparib) is a
first-in-class PARP inhibitor and the first targeted treatment to
potentially exploit DNA damage response (DDR) pathway deficiencies,
such as BRCA mutations, to preferentially kill cancer
cells. Specifically, in vitro studies have shown
that Lynparza-induced cytotoxicity may involve inhibition of
PARP-enzymatic activity and increased formation of PARP-DNA
complexes, resulting in DNA damage and cancer cell
death. Lynparza is being tested in a range of DDR-deficient
tumour types.
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 20,000 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 ovarian cancer
Ovarian
cancer is a leading cause of cancer death in women worldwide, with
a five-year survival rate of 19%.i In 2018, there
were over 295,000 new cases diagnosed and around 184,799
deaths.ii For
newly-diagnosed advanced ovarian cancer, the primary aim of
treatment is to delay progression of the disease for as long as
possible and maintain the patient's quality of life with the intent
of achieving complete remission or cure.iii,iv,v,vi
About 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.
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 a key growth driver for
AstraZeneca 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 &
Metabolism and Respiratory. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide.
For more information, please visit www.astrazeneca.com and follow
us on Twitter @AstraZeneca.
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Adrian Kemp
Company Secretary
AstraZeneca PLC
i American Cancer Society. Survival
Rates for Ovarian Cancer, by Stage. Available at:
https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html.
Accessed: October 2018
ii Globocan 2018
http://gco.iarc.fr/
iii Moore
K et al. Maintenance Olaparib in Patients with Newly Diagnosed
Advanced Ovarian Cancer. Presented at ESMO October
2018
iv Raja,
F. A., Chopra, N. & Ledermann, J. A. Optimal first-line
treatment in ovarian cancer. Ann. Oncol. Off. J. Eur. Soc. Med.
Oncol. 23 Suppl 10, x118-127 (2012
v NHS
Choices, Ovarian Cancer Accessed
https://www.nhs.uk/conditions/ovarian-cancer/treatment/ in
September 2018
vi Ledermann.et al. 2013.
Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO
Clinical Practice.
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:
22 October 2018
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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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