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
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1. FDA
panel backs Lynparza use for pancreatic cancer
17 December 2019 18:00 GMT
Lynparza recommended by FDA advisory committee for
1st-line maintenance treatment of germline BRCA-mutated metastatic
pancreatic cancer
ODAC voted that Lynparza demonstrated a clinically meaningful and
favourable risk-benefit
profile for patients based on Phase III POLO trial
results
AstraZeneca and MSD Inc., Kenilworth, NJ, US (MSD: known as Merck
& Co., Inc. inside the US and Canada) today announced that the
US Food and Drug Administration (FDA) Oncologic Drugs Advisory
Committee (ODAC) voted 7 to 5 to recommend Lynparza (olaparib) as a 1st-line
maintenance monotherapy for patients with germline BRCA-mutated
(gBRCAm) metastatic adenocarcinoma of the pancreas (pancreatic
cancer), whose disease has not progressed following 1st-line
platinum-based chemotherapy.
In August 2019, the FDA accepted the supplemental New Drug
Application (sNDA) for Lynparza for this indication with Priority Review and
set a Prescription Drug User Fee Act (PDUFA) date for
the fourth quarter of 2019.
José
Baselga, Executive Vice President, Oncology R&D,
said: "We
are pleased with the ODAC's recommendation for Lynparza and the potential to
bring a personalised, biomarker-targeted medicine to patients with
germline BRCA-mutated metastatic pancreatic cancer. Patients with
advanced pancreatic cancer historically have faced poor outcomes
due to the aggressive nature of the disease and limited treatment
advances over the last few decades. We look forward to working with
the FDA as it completes the review of our
application."
Roy
Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "We are encouraged by the ODAC's favourable vote
for Lynparza as
a 1st-line maintenance therapy in
germline BRCA-mutated metastatic pancreatic cancer.
This recommendation is a significant step towards
reaching our goal to help patients with this deadly
disease."
The sNDA submission was based on the positive results from the
Phase III POLO trial published in The
New England Journal of Medicine and presented at the 2019
American Society of Clinical Oncology Annual Meeting. The results showed a statistically significant
and clinically meaningful improvement in progression-free survival
and reduced the risk of disease progression or death by 47% based
on a hazard ratio of 0.53 (p=0.0038). Lynparza nearly doubled the time patients with gBRCAm
metastatic pancreatic cancer lived without disease progression or
death to a median of 7.4 months vs. 3.8 months on
placebo.
The benefit of maintenance with Lynparza was seen consistently across a range of
clinically meaningful endpoints. At each time point, from six
months onwards, more than twice as many patients treated
with Lynparza showed no disease progression vs. those on
placebo. In patients with measurable disease at baseline, 23%
responded to Lynparza vs.12% on placebo and had a median duration
of treatment in excess of two years (24.9 months) vs 3.7 months on
placebo. Overall survival (OS), a secondary endpoint, at interim
analysis was 18.9 months for Lynparza vs. 18.1 months for placebo but did not
reach statistical significance (HR=0.90; p=0.68). The safety
and tolerability profile of Lynparza in the Phase III POLO trial was in line with
that observed in prior clinical trials.
The
ODAC provides the FDA with independent, expert advice and
recommendations on marketed and
potential new medicines for use in the treatment of cancer. The FDA
will consider the vote as it reviews the submission and is not
bound by the Committee's recommendation.
In addition to the US, Lynparza is currently under regulatory review in the
EU, Canada and other jurisdictions as a 1st-line maintenance
treatment for patients with gBRCAm metastatic pancreatic
cancer.
Pancreatic
cancer is a rare, life-threatening disease that accounts for
about 3% of all cancers in the US. The FDA
granted Lynparza Orphan
Drug Designation in October
2018, which is for medicines intended to treat, diagnose or
prevent rare diseases or disorders that affect fewer than 200,000
people in the US.
Lynparza was the first PARP inhibitor to be approved
and has been used in over 25,000 patients
worldwide. Lynparza is currently approved in
65 countries including the US 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.
About pancreatic cancer
Pancreatic cancer is a deadly cancer with a high unmet medical
need. It is the 12th most commonly occurring
cancer2 and
the 7th leading cause of cancer death globally.3 The
disease has the lowest survival rate of the most common
cancers4,5 and
is the only major cancer with a single-digit five-year survival
rate (2-9%) in nearly every country.5 There were
approximately 460,000 new cases worldwide in
20186. As there
are often no symptoms, or symptoms may be non-specific in the early
stages7,
it is most commonly diagnosed at an incurable
stage.8 Around
80% of pancreatic cancer patients are diagnosed when the disease
has metastasised and for these the average survival is less than a
year.9 Despite advances
in treatment10,
few improvements have been made in diagnosis and treatment over the
decades.11,12 Current treatment
is surgery (for which approximately only 10-20% of patients are
eligible), chemotherapy and radiotherapy, highlighting a critical
unmet medical need for more effective treatment
options.13
About POLO
POLO is a Phase III randomised, double-blinded, placebo-controlled,
multi-centre trial of Lynparza tablets (300mg twice daily) as maintenance
monotherapy vs. placebo. The trial randomised 154 patients with
gBRCAm 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
overall survival, time to second disease progression, overall
response rate and health-related quality of
life.1
The results showed a statistically significant and clinically
meaningful improvement in progression-free survival,
where Lynparza nearly doubled the time patients with gBRCAm
metastatic pancreatic cancer lived without disease progression or
death to a median of 7.4 months vs. 3.8 months on placebo and
reduced the risk of disease progression or death by 47% (HR 0.53
[95% CI, 0.35-0.82], p=0.004). The benefit of maintenance
with Lynparza was seen consistently across a range of
clinically meaningful endpoints. From six months onwards, more than
twice as many patients receiving Lynparza showed no disease progression vs. those
receiving placebo. In patients with measurable disease at baseline,
23% responded to Lynparza vs.12% on placebo (odds ratio, 2.30; 95% CI,
0.89 to 6.76) and had a median duration of treatment in excess of
two years (24.9 months; 95% CI, 14.8 to could not be calculated) vs
3.7 months on placebo (95% CI, 2.1 to could not be calculated).
Overall survival (OS), a secondary endpoint, at interim analysis
was 18.9 months for Lynparza vs. 18.1 months for placebo but did not
reach statistical significance (HR=0.90;
p=0.68).
The safety and tolerability profile of Lynparza in the POLO trial was in line with that
observed in prior clinical trials. The most common adverse events
(AEs) ≥20% were fatigue/asthenia (60%), nausea (45%),
abdominal pain (29%), diarrhoea (29%), anaemia (28%), decreased
appetite (25%) and constipation (23%). The most common ≥
grade 3 AEs were anaemia (11%), fatigue/asthenia (5%), decreased
appetite (3%), abdominal pain (2%), vomiting (1%) and arthralgia
(1%). AEs led to dose reduction in 16% of patients
on Lynparza while 5% of patients discontinued
treatment.
There
are currently no precision medicine treatment options for gBRCAm
pancreatic cancer patients. However, based on the results of POLO,
the National Comprehensive Cancer Network (NCCN) guidelines were
updated in July 2019 to
recommend Lynparza as
maintenance treatment for gBRCAm pancreatic cancer.14
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.
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, 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 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, prostate
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, the
Company is committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
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 (LSE/STO/NYSE: 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 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.
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References
1. Golan et al (2019). Maintenance Olaparib for Germline
BRCA-Mutated Metastatic Pancreatic Cancer. New England Journal of
Medicine.
2. World Cancer Research Fund
International. Pancreatic cancer statistics. Available
at: www.wcrf.org/dietandcancer/cancer-trends/pancreatic-cancer-statistics Accessed
October 2019.
3. World Health Organization. IARC.
(2019). Estimated number of deaths in 2018, worldwide, both sexes,
all ages. Website available here.
Accessed October 2019.
4. Pancreaticcancer.org.uk. Pancreatic
cancer statistics. Available at: www.pancreaticcancer.org.uk/statistics/ Accessed
October 2019.
5. Worldpancreaticcancerday.org.
Available at: www.worldpancreaticcancerday.org/about-pancreatic-cancer/ Accessed
October 2019.
6. World Health Organization. IARC.
(2019). Estimated number of new cases in 2018, worldwide, both
sexes, all ages. Website available here.
Accessed October 2019.
7. Pancreaticcancer.org.uk. Signs and
symptoms of pancreatic cancer. Available
at: www.pancreaticcancer.org.uk/information-and-support/facts-about-pancreatic-cancer/signs-and-symptoms-of-pancreatic-cancer/ Accessed
October 2019.
8. DaVee (2018). Pancreatic cancer
screening in high-risk individuals with germline genetic
mutations. Gastrointestinal
Endoscopy. 87(6),
pp.1443-1450.
9. Azar et al. (2019). Treatment and survival rates of
stage IV pancreatic cancer at VA hospitals: a nation-wide
study. Journal of Gastrointestinal
Oncology, 10(4),
pp.703-711.
10. Sheahan et al. (2018). Targeted therapies in the management of
locally advanced and metastatic pancreatic cancer: a systematic
review. Oncotarget. 9(30): 21613-21627.
11. Adamska et al. (2017). Pancreatic ductal adenocarcinoma:
current and evolving therapies. International Journal of
Molecular Science. 18(7):
1338.
12. Yongxing et al. (2017). Molecular subtyping of pancreatic
cancer: translating genomics and transcriptomics into the
clinic. Journal of
Cancer. 8(4):513-522.
13. Stunt, A. (2016). Pancreatic cancer: GPs
can help prognosis by identifying early signs. Guidelines in
Practice. Available at: www.guidelinesinpractice.co.uk/cancer/pancreatic-cancer-gps-can-help-prognosis-by-identifying-early-signs/352855.article Accessed
October 2019.
14. NCCN. (2019). NCCN Guidelines for
Patients® | Pancreatic Cancer. Nccn.org. Available
at: https://www.nccn.org/patients/guidelines/pancreatic/12/ Accessed
December 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:
17 December
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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