AstraZeneca PLC (AZN) - Top-line phase III results for Naloxegol
RNS Number : 8525Q
12 November 2012
ASTRAZENECA ANNOUNCES TOP-LINE PHASE III RESULTS
FROM NALOXEGOL PIVOTAL TRIALS IN PATIENTS WITH
AstraZeneca today announced positive top-line results from two Phase III
trials and one safety extension trial in patients with non-cancer related pain
and opioid-induced constipation (OIC). These Phase III KODIAC trials evaluated
the safety and efficacy of naloxegol, an oral peripherally-acting, mu-opioid
receptor antagonist for the treatment of OIC, a common side effect of
KODIAC-04 and -05 are both multicenter, randomized, double-blind,
placebo-controlled pivotal trials of 12 weeks duration evaluating 12.5 mg and
25 mg naloxegol administered once-daily. The primary endpoint in both trials
was percentage of OIC responders versus placebo over 12 weeks of treatment
where a responder was defined as having at least three Spontaneous Bowel
Movements (SBM) per week, with at least one SBM per week increase over
baseline, for at least nine out of 12 weeks, and at least three out of the
last four weeks. Under the design of both trials, statistical significance for
the primary endpoint would be achieved if at least one of the two naloxegol
doses had a p-value <0.025 compared with placebo.
Analysis of the data indicates that in KODIAC-04 both naloxegol doses (12.5 mg
and 25 mg) demonstrated statistically significant results for the primary
endpoint. P-values were 0.015 and 0.001 respectively.
In KODIAC-05, the 25 mg dose demonstrated a statistically significant result
for the primary endpoint but the 12.5 mg dose did not. P-values were 0.202 for
12.5 mg and 0.021 for 25 mg.
The analyses also showed no clinically relevant imbalances in serious adverse
events (SAEs), including externally adjudicated major cardiovascular events,
across the three treatment arms in KODIAC-04, -05 and -07. The most common
adverse events (AEs) in the naloxegol treatment arms in both trials were
abdominal pain, diarrhea and nausea. In KODIAC-07, (the safety extension of
KODIAC-04) the occurrence of AEs and SAEs was lower than in KODIAC-04 and -05.
Among non serious adverse events, arthralgia was the most common and was
reported only in patients in the naloxegol 25 mg arm. All other common AEs
were distributed similarly across the three treatment arms. In KODIAC-04 and
-05 for either naloxegol dose, compared to placebo, there were no significant
differences in change from baseline in mean daily pain scores or mean total
daily opioid dose. A full assessment of the safety and tolerability findings
of all three studies is ongoing.
Naloxegol is part of the exclusive worldwide license agreement announced on 21
September 2009 between AstraZeneca and Nektar Therapeutics.
"Opioid-induced constipationis a burdensome condition which is often
overlooked, inadequately managed and can negatively impact a patient's quality
of life," said Martin Mackay, President of Research and Development,
AstraZeneca. "The top-line results of the pivotal KODIAC studies provide
important new information on the safety and efficacy of naloxegol as a
potential treatment for opioid-induced constipation and we are looking forward
to advancing this programme."
The core Phase III KODIAC programme for naloxegol is comprised of four
clinical trials which are designed to investigate the safety and efficacy of
naloxegol for the treatment of OIC in patients with non-cancer related pain.
The full data from these trials will be submitted for presentation at future
The three trials reporting top-line results today include KODIAC-04, -05, and
-07. KODIAC-04 and -05 are replicate pivotal 12-week efficacy and safety
trials, while KODIAC-07 is a 12-week safety extension of KODIAC-04. After
initial locking of the database for KODIAC-05, data associated with one
patient that was previously assessed as non-retrievable was found to be
retrievable. These data were added to the database and the database was again
locked and underwent a final analysis. All three trials were conducted in
patients with non-cancer pain and documented OIC, who require daily opioid
Enrolment is complete for the open-label, randomized, 52-week long-term safety
trial (KODIAC-08) and the trial is expected to be completed by Q1 2013.
Naloxegol is currently considered a Schedule II controlled substance by the US
Drug Enforcement Administration (DEA) based on structural relatedness to
noroxymorphone. AstraZeneca has conducted the studies necessary to evaluate
the abuse potential and dependence-producing properties of naloxegol in
support of obtaining decontrol. A petition for the decontrol of naloxegol was
submitted to the DEA in March 2012 and subsequently accepted for review.
Commercialisation and launch in the US will be subject to both FDA approval
and DEA schedule determination.
NOTES TO EDITORS
Naloxegol is a peripherally-acting mu-opioid receptor antagonist being
investigated for the treatment of constipation (opioid-induced constipation or
OIC) as a side effect of prescription opioid pain medicines.
Top-line results of the Phase II study of naloxegol (formerly NKTR-118) were
previously presented at the American College of Gastroenterology Annual
Clinical Meeting and the American Academy of Pain Management Annual Meeting.
Naloxegol was developed using Nektar's oral small molecule polymer conjugate
About Opioid-Induced Constipation
Opioids attach to specific proteins called opioid receptors. When the opioids
attach to certain opioid receptorsin the gastrointestinal tract, constipation
may occur. Opioid-induced constipation (OIC) is a result of decreased fluid
absorption and lower gastrointestinal motility due to opioid receptor binding
in the gastrointestinal tract.
Globally, approximately 40-50% (28-35 million) patients taking opioids for
long-term pain develop constipation. About 40-50% (11-18 million) of those OIC
sufferers achieve the desired treatment outcomes with current options that
include over-the-counter and prescription laxatives.
Nektar Therapeutics (NASDAQ: NKTR) is a clinical-stage biopharmaceutical
company developing novel therapeutics based on its PEGylation and advanced
polymer conjugate technology platforms. Nektar has a robust R&D pipeline of
therapeutic candidates in oncology, pain and other areas. The company is
headquartered in San Francisco, California, with additional R&D operations in
Huntsville, Alabama and Hyderabad, India. Further information about Nektar and
its drug development programs and capabilities may be found online at
AstraZeneca is a global, innovation-driven biopharmaceutical business with a
primary focus on the discovery, development and commercialization of
prescription medicines for gastrointestinal, cardiovascular, neuroscience,
respiratory and inflammation, oncology and infectious disease. AstraZeneca
operates in over 100 countries and its innovative medicines are used by
millions of patients worldwide. For more information please visit:
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12 November 2012
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MSCQLLBFLFFLFBB -0- Nov/12/2012 07:01 GMT
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