AstraZeneca
PLC
INDEX TO
EXHIBITS
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1.
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Press release
entitled, “Phase III head to head trial showed ticagrelor reduced
cardiovascular death and heart attacks over clopidogrel in
acute coronary syndromes patients”, dated 1 September
2009.
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2.
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Press release
entitled, “Transparency Directive Voting Rights and Capital”, dated 1
September 2009.
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3.
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Press release
entitled, “Transaction by Persons Discharging Managerial Responsibilities
Disclosure Rule DTR 3.1.4”, dated 1 September 2009.
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4.
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Press release
entitled, “Publication of Prospectus”, dated 4 September
2009.
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5.
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Press release
entitled, “Transaction by Persons Discharging Managerial Responsibilities
Disclosure Rule DTR 3.1.4”, dated 8 September 2009.
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6.
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Press release
entitled, “AstraZeneca and Nektar sign worldwide agreement for Nektar drug
development programmes to address opioid-induced constipation”, dated 21
September 2009.
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7.
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Press release
entitled, “US Court of Appeals affirms summary judgment decision in
SEROQUEL patent litigation”, dated 28 September
2009.
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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.
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AstraZeneca
PLC |
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Date:
2 October 2009
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By:
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/s/ Adrian
Kemp |
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Name: |
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Title:
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Company
Secretary
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Item 1
PHASE
III HEAD TO HEAD TRIAL SHOWED TICAGRELOR REDUCED
CARDIOVASCULAR
DEATH AND HEART ATTACKS OVER CLOPIDOGREL
IN
ACUTE CORONARY SYNDROMES PATIENTS
EFFICACY RESULTS
ACHIEVED WITH NO INCREASE IN MAJOR BLEEDING
AstraZeneca today announced results
from the phase III head to head trial, PLATO (A Study of Platelet Inhibition and
Patient Outcomes), which demonstrate that ticagrelor (BRILINTA™) has achieved
greater efficacy in the primary endpoint, reduction of cardiovascular events (CV
death, MI, stroke) over clopidogrel (Plavix®/Iscover®) (9.8% vs. 11.7% at 12
months; 16% RRR; 95% CI, 0.77 to 0.92; p<0.001), without an increase in major
bleeding (11.6% vs. 11.2%, p=0.43). This efficacy endpoint was driven by a
statistically significant reduction in both CV death (4.0% vs. 5.1%, p=0.001)
and heart attacks (myocardial infarction, MI) (5.8% vs. 6.9%, p=0.005) with no
difference in stroke (1.5% vs. 1.3%, p=0.22). Ticagrelor is the first
investigational antiplatelet that has demonstrated a reduction in CV death
versus clopidogrel in patients with acute coronary syndromes (ACS). Primary
results from the PLATO study were presented today at the European Society of
Cardiology congress and simultaneously published in the New England Journal
of Medicine (NEJM), www.nejm.com.
For patients in the
PLATO study, the reduction in risk of cardiovascular events with ticagrelor
occurred early and this benefit increased over time compared to clopidogrel.
Ticagrelor demonstrated a consistent positive effect across multiple secondary
efficacy endpoints including CV death (and separately for all-cause mortality);
myocardial infarction; the composite of myocardial infarction, stroke, and
all-cause mortality. Among patients who received a stent during the study, a 33%
reduction in risk of definite stent thrombosis was achieved with
ticagrelor.
“The goal of new
antiplatelet therapies is to improve the efficacy for patients without
increasing the associated risks of treatment such as bleeding. Ticagrelor
achieved a significant reduction in CV mortality in ACS patients versus
clopidogrel and importantly without an increase in major bleeding,” commented
Professor Lars Wallentin, co-chair of the PLATO Executive Committee, Uppsala
Clinical Research Centre.
AstraZeneca
Executive Vice-President Development, Anders Ekblom said, “The PLATO study was
designed to reflect how patients with ACS are currently managed in clinical
practice, by including patients who underwent invasive procedures and those who
were managed with medication only. The PLATO data suggest ticagrelor could be a
valuable new option for a broad range of acute coronary syndromes patients. We
look forward to filing BRILINTA with regulatory authorities in the fourth
quarter.”
The PLATO study
confirmed the clinical safety profile of previous ticagrelor studies which
showed no difference in major bleeding compared to clopidogrel. When PLATO minor
bleeding was added to the major bleeding results, ticagrelor showed an increase
versus clopidogrel (16.1% vs. 14.6%, p=0.008). There was also an increase in
non-procedural related bleeding with ticagrelor. Within the patient subgroups of
gender, weight, history of stroke/TIA, ticagrelor showed no increase in the
incidence of major bleeding versus clopidogrel.
Consistent with
phase II data, ventricular pauses (slowing of heart rhythms) occurred more often
with ticagrelor but without associated symptoms or clinical consequences for the
patient. Dyspnoea was reported more frequently by patients on ticagrelor (13.8%
vs. 7.8%, p<0.001) but did not represent new or worsening heart failure or
lung disease. Only one in 100 ticagrelor patients overall stopped taking study
medication due to dyspnoea.
PLATO analysed 66
subgroups (33 efficacy and 33 safety subgroups). Thirty of the 33 efficacy
subgroups analysed were consistent with the analysis of efficacy in the overall
population; showing a benefit for ticagrelor over clopidogrel. Of the
three remaining subgroups, one (patients with weight below the gender-specific
median) showed an attenuated benefit for ticagrelor over clopidogrel. The other
two subgroups (patients not taking a statin medication on the day of
randomisation and those at sites in North America) showed no treatment advantage
for ticagrelor.
Of the 33 safety
subgroups analysed, 32 were consistent with the analysis of safety in the
overall population; showing no statistically significant difference between
ticagrelor and clopidogrel. The remaining subgroup (patients with a
Body Mass Index BMI >30kg/m2) had major bleeding more frequently with
ticagrelor than with clopidogrel.
Given the large
number of tests performed these differences may have been due to chance. The
observed difference in results between patients in North America and those
enrolled elsewhere raises questions of whether geographic differences between
populations of patients or practice patterns influenced the effects of the
randomised treatments, although no apparent explanations have been found to
date.
“As a cardiology
community, we are constantly seeking rigorously studied options to offer our
patients who are facing an increased risk of serious, and potentially deadly,
complications," said Robert A. Harrington, M.D, co-chair of the PLATO Executive
Committee, Duke Clinical Research Institute. “An estimated one in three ACS
patients will die, have a recurrent heart attack or be readmitted to hospital
within six months of their first cardiovascular event, so preventing
reoccurrence is vital in ACS patient treatment.”
The PLATO results
have confirmed AstraZeneca’s intention to submit the NDA and MAA with regulatory
agencies during the fourth quarter of this year.
PLATO was a
head-to-head 18,624 patient outcomes study of ticagrelor plus aspirin versus the
active comparator, clopidogrel plus aspirin, and was designed to establish
whether ticagrelor could achieve meaningful cardiovascular and safety endpoints
in ACS patients. Given the size of the PLATO database, we will continue to
analyse and publish additional PLATO findings.
NOTES
TO EDITORS:
Primary results
from the PLATO study were presented today at the European Society of Cardiology
annual meeting in Barcelona, Spain and simultaneously published in the online
version of the New England Journal of Medicine (NEJM), www.nejm.com.
About BRILINTATM
Ticagrelor
(BRILINTA™) is an investigational oral antiplatelet treatment for ACS. BRILINTA
(ticagrelor) is the first reversibly binding oral adenosine diphosphate (ADP)
receptor antagonist. It selectively inhibits P2Y12,
a key target receptor for ADP. ADP receptor blockade inhibits the action of
platelets in the blood, reducing recurrent thrombotic events.
BRILINTA is the
first in a new chemical class, the CPTPs (cyclo-pentyl-triazolo-pyrimidines) and
is chemically distinct from the thienopyridines, such as clopidogrel and
prasugrel.
AstraZeneca has
proposed the name BRILINTATM.
If approved by the FDA and the EMEA, it will serve as the trade name for
ticagrelor. BRILINTA is a trademark of the AstraZeneca group of
companies.
About
the PLATO study
PLATO was an international
head-to-head outcomes study of ticagrelor plus aspirin, versus clopidogrel
plus aspirin. The PLATO study was designed to establish whether
ticagrelor could achieve clinically meaningful cardiovascular and safety
endpoints in ACS patients, above and beyond those afforded by clopidogrel, an
irreversible therapy in the thienopyridine class of medicines.
The study design of
PLATO was published in the April 2009 edition of the American Heart
Journal.
PLATO
Bleeding Definitions:
The bleeding definitions used
within the PLATO trial were an evolution from the CURE bleeding definitions and
were developed by the PLATO Executive Committee as constituting the most
appropriate and clinically meaningful assessment of bleeding complications
associated with acute and chronic therapy. The PLATO bleeding definitions
provide a framework to allow investigators to record all bleeding events
reported by patients in the PLATO trial. The bleeding definitions were developed
to characterise bleeding in both the acute and long-term setting.
PLATO
Secondary Endpoints Results:
CV death (4.0% vs.
5.1%, p=0.001); Separately for all-cause mortality (4.5% vs. 5.9% with
clopidogrel; p<0.001); myocardial infarction (5.8% vs. 6.9%, p=0.005); the
composite of myocardial infarction, stroke, and all-cause mortality (10.2% vs.
12.3%, p<0.001); and a composite of cardiovascular death, myocardial
infarction, stroke, transient ischemic attack, recurrent cardiac ischemia,
severe recurrent cardiac ischemia, and other arterial thrombotic events (14.6%
vs. 16.7%, p<0.001).
About
AstraZeneca
AstraZeneca is a
major international healthcare business engaged in the research, development,
manufacturing and marketing of meaningful prescription medicines and supplier
for healthcare services. AstraZeneca is one of the world's leading
pharmaceutical companies with healthcare sales of US$ 31.6 billion and is a
leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology
and infectious disease medicines. For more information about
AstraZeneca, please visit: www.astrazeneca.com.
CONTACTS:
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Enquiries EU:
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Enquiries US:
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Investor
Enquiries UK:
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Jonathan
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Investor
Enquiries US:
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Jorgen
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1 September
2009
Item 2
Transparency
Directive
Voting
Rights and Capital
The
following notification is made in accordance with the UK Financial Services
Authority Disclosure and Transparency Rule 5.6.1. On 31 August
2009 the issued share capital of AstraZeneca PLC with voting rights is
1,449,453,331 ordinary shares of US$0.25. No shares are held in
Treasury. Therefore, the total number of voting rights in AstraZeneca PLC is
1,449,453,331.
The
above figure for the total number of voting rights may be used by shareholders
as the denominator for the calculations by which they will determine if they are
required to notify their interest in, or a change to their interest in,
AstraZeneca PLC under the FSA's Disclosure and Transparency
Rules.
A
C N Kemp
Company
Secretary
1
September 2009
Item 3
Transaction
by Persons Discharging Managerial Responsibilities
Disclosure
Rule DTR 3.1.4
We hereby inform
you that on 31 August 2009, Michele Hooper, a Director of the Company, notified
us that, on 31 August 2009, she purchased 1,200 AstraZeneca American Depositary
Shares (ADSs) at a price of $47.08 per share. One AstraZeneca ADS
equals one AstraZeneca PLC Ordinary Share of USD0.25.
Following this
purchase, Michele Hooper has a total interest in 1,700 shares, which represents
approximately 0.0001% of the issued ordinary capital of the
Company.
A
C N Kemp
Company
Secretary
1
September 2009
Item
4
Publication
of Prospectus
AstraZeneca
PLC has published the attached prospectus dated 4 September 2009 in respect of
its US$5,000,000,000 Euro Medium Term Note Programme.
http://www.rns-pdf.londonstockexchange.com/rns/5848Y_-2009-9-4.pdf
The Prospectus is
available to the public for inspection at the following addresses:
Document Viewing
Facility
UK
Listing Authority
25
The North Colonnade
Canary
Wharf
London E14
5HS
AstraZeneca
PLC
15
Stanhope Gate
London W1K
1LN
A
C N Kemp
Company
Secretary
4
September 2009
Please
note that the prospectus contains restrictions on the sale of the securities
described therein to persons in certain jurisdictions and that the prospectus is
not addressed to such persons, nor should such persons use or rely on the
information contained therein.
Item 5
Transaction
by Person Discharging Managerial Responsibilities
Disclosure
Rules DTR 3.1.4R
We hereby inform
you that the interest of Bruno Angelici, a person discharging managerial
responsibility, in the shares of AstraZeneca PLC has changed as detailed
below.
On 7 September
2009, Mr Angelici exercised an option over 37,728 AstraZeneca PLC Ordinary
Shares at an option price of £22.31 per share. The option was granted
to Mr Angelici in March 2003.
Following the
exercise, Mr Angelici sold all of the 37,728 shares so acquired at a price of
£27.95 per share.
A
C N Kemp
Company
Secretary
8
September 2009
Item
6
ASTRAZENECA
AND NEKTAR SIGN WORLDWIDE AGREEMENT FOR NEKTAR DRUG DEVELOPMENT PROGRAMMES TO
ADDRESS OPIOID-INDUCED CONSTIPATION
AstraZeneca and
Nektar Therapeutics announced today that they have entered into an exclusive
worldwide license agreement for two drug development programmes: NKTR-118, a
late stage investigational product being evaluated for the treatment of
opioid-induced constipation, and the NKTR-119 programme, an early stage
programme that is intended to deliver products for the treatment of pain without
constipation side effects. Both programmes were developed by Nektar,
utilizing their proprietary small molecule advanced polymer conjugate technology
platform.
Under the terms of
the agreement, AstraZeneca will assume the responsibility for the continued
development of both the NKTR-118 and NKTR-119 programmes, including the
initiation of late-stage clinical studies for NKTR-118. AstraZeneca
expects completion of the design of the phase III programme in the near term,
and anticipates filing the drug with regulators in 2013. AstraZeneca
will also be responsible for global manufacturing and marketing for both
programmes. Under the agreement, Nektar will receive an upfront
payment of $125 million for both NKTR-118 and NKTR-119.
NKTR-118 has
completed a Phase 2 clinical trial and is being developed to treat constipation
caused by the use of opioid pain products. Under the agreement, for NKTR-118,
Nektar is eligible to receive up to $235 million in aggregate payments upon the
achievement of certain regulatory milestones, as well as additional tiered sales
milestone payments of up to $375 million if the product achieves considerable
levels of commercial success. Nektar will also be eligible to receive
significant double-digit royalty payments on net sales of NKTR-118
worldwide.
NKTR-119 is an
early stage drug development programme that is intended to combine oral NKTR-118
with selected opioids, with the goal of treating pain without the side effect of
constipation traditionally associated with opioid
therapy. AstraZeneca will continue the development of this programme,
including determining the appropriate opioid combinations with
NKTR-118. For NKTR-119, Nektar would receive development milestone
payments as well as tiered sales milestone payments. Nektar will also
receive significant double-digit royalty payments on NKTR-119 net sales
worldwide.
“NKTR-118 is an
important late stage programme that has the potential to address a real need for
patients,” said David Brennan, Chief Executive Officer of
AstraZeneca. “We are excited about this agreement with Nektar, as it
provides us the opportunity to apply our deep knowledge and expertise in
neuroscience, oncology and gastrointestinal areas of medicine to create real
value for patients. This is a good example of using externalisation to enrich
the company’s late-stage pipeline.”
“We are extremely
pleased to enter into this exclusive global license agreement with AstraZeneca,”
said Howard W. Robin, President and Chief Executive Officer of Nektar
Therapeutics. “AstraZeneca has a strong history of creating and establishing
market-leading brands, which makes them the ideal development and commercial
partner for our NKTR-118 and NKTR-119 programmes. In addition to the
promise that these potential products provide to patients, this partnership
validates Nektar’s successful strategy to create novel oral small molecule drug
candidates with our advanced polymer conjugate technology
platform.”
NKTR-118 is an
investigational drug candidate that combines Nektar's advanced small molecule
polymer conjugate technology platform with naloxol, a derivative of the
opioid-antagonist drug, naloxone. Results from NKTR-118’s Phase 2
clinical trial will be presented at an oral plenary session of the American
College of Gastroenterology 2009 Annual Scientific Meeting in
October.
The agreement is
subject to review by the United States Government under the Hart-Scott Rodino
Act and becomes effective after the expiration or earlier termination of the
waiting period (or any extension thereof).
NOTES
TO EDITORS:
About
Opioid Induced Constipation
It is estimated
that for those patients who take opiates chronically for pain management,
anywhere from 40-90% of such patients will develop constipation. Less
than half of those patients find effective relief from current treatment options
that include prescription and over-the-counter laxatives and stool softeners.
These symptoms of bowel dysfunction are a result of the drug binding to the
mu-opioid receptor in the gut(1). Opioid-induced bowel dysfunction
encompasses symptoms such as constipation, bloating, abdominal cramping, and
gastroesophageal reflux. Constipation is the hallmark of this syndrome and is
generally its most prominent component.
According to IMS
Health, about 230 million prescriptions were written for opioids in 2007 in the
United States alone. This is estimated to represent about 65-75% of the
worldwide opioid market. Currently, there are no oral drugs approved
that are indicated to treat opioid-induced constipation. Opioid bowel
dysfunction and opioid-induced constipation can significantly impact quality of
life and increase healthcare utilisation.
About
Nektar
Nektar Therapeutics
is a biopharmaceutical company developing novel therapeutics based on its
PEGylation and advanced polymer conjugation technology
platforms. Nektar's technology and drug development expertise have
enabled nine approved products in the U.S. or Europe for partners, which include
leading biopharmaceutical companies, including UCB's Cimzia®, Roche's PEGASYS®
for hepatitis C and Amgen's Neulasta® for
neutropenia. Nektar
has created a robust pipeline of potentially high-value therapeutics to address
unmet medical needs by leveraging and expanding its technology platforms to
improve and enable molecules. Nektar is currently conducting clinical
and preclinical programmes in oncology, pain and other therapeutic
areas. NKTR-102, PEGylated irinotecan, is currently in Phase 2
clinical studies in ovarian, breast and colorectal cancer. NKTR-105,
PEGylated docetaxel, is currently in a Phase 1 clinical study in patients with
refractory solid tumors.
Nektar is
headquartered in San Carlos, California, with additional R&D operations in
Huntsville, Alabama and Hyderabad, India. Further information about
the company and its drug development programmes and capabilities may be found
online at http://www.nektar.com.
About
AstraZeneca
AstraZeneca is a major international
healthcare business engaged in the research, development, manufacturing and
marketing of meaningful prescription medicines and supplier for healthcare
services. AstraZeneca is one of the world's leading pharmaceutical companies
with healthcare sales of US$ 31.6 billion and is a leader in gastrointestinal,
cardiovascular, neuroscience, respiratory, oncology and infectious disease
medicines. For more information about AstraZeneca, please visit:
www.astrazeneca.com
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Media
Enquiries:
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Chris
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+44 207 304
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(24
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Neil
McCrae
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+44 207 304
5045
(24
hours)
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Sarah
Lindgreen
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+44 20 7304
5033
(24
hours)
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Emily Denney
(US)
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+1 302 885
3451
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Investor
Enquiries UK:
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Jonathan
Hunt
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+44 207 304
5087
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mob:+44 7775
704032
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Karl
Hard
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+44 207 304
5322
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mob:+44 7789
654364
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Investor
Enquiries US:
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Ed
Seage
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+1 302 886
4065
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mob: +1 302
373 1361
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Jorgen
Winroth
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+1 212 579
0506
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mob: +1 917
612 4043
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21 September
2009
Item 7
US
COURT OF APPEALS AFFIRMS SUMMARY JUDGMENT DECISION IN SEROQUEL PATENT
LITIGATION
AstraZeneca today
announced that the US Court of Appeals for the Federal Circuit has affirmed the
Summary Judgment decision of No Inequitable Conduct in patent litigation
involving SEROQUEL (quetiapine fumarate) tablets. In July 2008,
AstraZeneca announced that the US District Court for the District of New Jersey
granted the company's Motion for Summary Judgment of No Inequitable Conduct in
litigation involving Teva Pharmaceutical Industries Ltd. and Sandoz,
Inc.
This most recent
decision, made public on 25 September 2009, upholds the District Court’s
judgment that Teva’s and Sandoz’s products will infringe AstraZeneca’s SEROQUEL
patent and that the patent is valid and enforceable. AstraZeneca had sued Teva
Pharmaceutical Industries Ltd. and Sandoz, Inc. alleging infringement of
AstraZeneca’s patent as a result of Teva’s and Sandoz’s filings of Abbreviated
New Drug Applications (ANDAs). Teva and Sandoz had conceded infringement and the
validity of AstraZeneca’s patent covering SEROQUEL. The ANDAs sought approval to
market generic versions of SEROQUEL tablets in the US before SEROQUEL’s patent
expires. The patent covering SEROQUEL expires in September 2011, with
paediatric exclusivity through March 2012.
Since the Federal
Circuit Court of Appeals’ affirmed Summary Judgment in favor of AstraZeneca,
trial remains unnecessary.
About
AstraZeneca
AstraZeneca is a
major international healthcare business engaged in the research, development,
manufacturing and marketing of meaningful prescription medicines and supplier
for healthcare services. AstraZeneca is one of the world's leading
pharmaceutical companies with healthcare sales of US$ 31.6 billion and is a
leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology
and infectious disease medicines. For more information about AstraZeneca,
please visit: www.astrazeneca.com.
|
Media
Enquiries:
|
|
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|
Chris
Sampson
|
+44 20 7304
5130
(24
hours)
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Neil
McCrae
|
+44 207 304
5045
(24
hours)
|
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Sarah
Lindgreen
|
+44 20 7304
5033
(24
hours)
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Kirsten
Evraire (US)
|
+ 1 302 885
0435
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Investor
Enquiries UK:
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Jonathan
Hunt
|
+44 207 304
5087
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mob:+44 7775
704032
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Karl
Hard
|
+44 207 304
5322
|
mob:+44 7789
654364
|
|
|
|
|
|
Investor
Enquiries US:
|
|
|
|
Ed
Seage
|
+1 302 886
4065
|
mob: +1 302
373 1361
|
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Jorgen
Winroth
|
+1 212 579
0506
|
mob: +1 917
612 4043
|
28
September 2009