Blueprint
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
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Report
of Foreign Issuer
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For the
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Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza receives
positive EU CHMP opinion for 1st
29 April 2019 07:00 BST
Lynparza receives
positive EU CHMP opinion for 1st-line
maintenance treatment
of BRCA-mutated advanced ovarian
cancer
AstraZeneca and MSD's Lynparza is the only PARP inhibitor to
demonstrate
an improvement in progression-free survival for patients in this
setting
AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck
& Co., Inc. inside the US and Canada) today announced that the
Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency has adopted a positive opinion,
recommending Lynparza(olaparib) as a 1st-line maintenance treatment
of BRCA-mutated advanced ovarian
cancer.
The recommendation is for the use of Lynparza tablets as a maintenance treatment of adult
patients with advanced (FIGO stages III and
IV) BRCA1/2-mutated (germline and/or somatic) high-grade
epithelial ovarian, fallopian tube or primary peritoneal cancer who
are in response (complete or partial) following completion of
first-line platinum-based chemotherapy.
Dave Fredrickson, Executive Vice President, Oncology, said: "There
remains a significant unmet need in the treatment of advanced
ovarian cancer as 70% of women globally relapse within the first
three years after their initial treatment. The results of SOLO-1
demonstrate the potential of using Lynparza earlier in the treatment pathway as a
maintenance therapy, and reinforce the importance of identifying a
patient's BRCA mutation status as soon as they are
diagnosed."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "Women with advanced ovarian cancer need and deserve new
treatment options. In the SOLO-1 trial, Lynparza demonstrated a significant progression-free
survival benefit as maintenance treatment for patients with
advanced BRCA-mutated ovarian cancer following response to
first-line platinum-based chemotherapy. If approved, this expanded
indication could change the way women in Europe
with BRCA-mutated advanced ovarian cancer are
treated."
The positive opinion is based on data from the pivotal
Phase III SOLO-1 trial which showed
that Lynparza reduced the risk of disease progression or
death by 70% vs. placebo following response to platinum-based
chemotherapy (HR 0.30 [95% CI 0.23-0.41], p<0.001). Of
those patients receiving Lynparza, 60.4% remained progression-free at 36 months vs.
26.9% of women in the placebo arm.
Lynparza is currently
approved in 64 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 as 1st-line
maintenance treatment of BRCAm advanced ovarian cancer following response to
platinum-based chemotherapy. It is also approved in 38 countries,
including the US, countries in the EU and Japan, for
germline BRCAm 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 both ovarian cancer and breast
cancer.
About SOLO-1
SOLO-1 was a Phase III randomised, double-blinded,
placebo-controlled, multicentre trial to evaluate the efficacy and
safety of Lynparza tablets (300mg twice daily) as 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 complete or partial
clinical 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.
The data were presented on 21 October 2018 at the Presidential
Symposium of the ESMO 2018 Congress in Munich, Germany and
published simultaneously online in the New
England Journal of Medicine.
Summary of PFSi,ii
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Lynparza (n=260)
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Placebo
(n=131)
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Number
of patients with event (%)iii
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102
(39)
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96
(73)
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Median
PFS (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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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. 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.
About ovarian cancer
Ovarian cancer is a leading cause of cancer death in women
worldwide, with a five-year survival rate of
19%.1 In
2018, there were over 295,000 new cases diagnosed and around
185,000 deaths.2 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.3,4,5,6
About BRCA mutations
Breast cancer susceptibility genes 1/2 (BRCA1 and BRCA2) are human genes that produce proteins
responsible for repairing damaged DNA and play an important role
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 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 tumour types with defects and
dependencies in the DDR.
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. On 26 February
2019, AstraZeneca and MSD announced that Lynparza became
the first PARP inhibitor to demonstrate benefit in
germline BRCAm metastatic pancreatic cancer in the Phase III
POLO trial.
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 &
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 astrazeneca.com and
follow us on Twitter@AstraZeneca.
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Media
Relations
|
|
|
|
Gonzalo
Viña
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|
+44 203
749 5916
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Rob
Skelding
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Oncology
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+44 203
749 5821
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Rebecca
Einhorn
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518 4122
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Kent
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749 5906
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Hursit
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Other
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203 749 5762
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Meixell
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US
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885 2677
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Investor
Relations
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Thomas
Kudsk Larsen
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+44 203
749 5712
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Wheeler
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749 5797
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Gruvris
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BioPharma
(cardiovascular, metabolism)
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+44 203
749 5711
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Stone
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BioPharma
(respiratory, renal)
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+44 203
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Afolabi
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Other
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+44 203
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Adrian Kemp
Company Secretary
AstraZeneca PLC
References
1. 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: March 2019
2. Globocan 2018 http://gco.iarc.fr/
3. Moore K et al. Maintenance Olaparib in Patients with Newly
Diagnosed Advanced Ovarian Cancer. Presented at ESMO October
2018
4. 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)
5. NHS Choices, Ovarian Cancer Accessed https://www.nhs.uk/conditions/ovarian-cancer/treatment/ in
September 2018
6. 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:
29 April
2019
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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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