AstraZeneca Announces Results From Long-Term Safety Trial Of Naloxegol In Patients With Opioid-Induced Constipation

  AstraZeneca Announces Results From Long-Term Safety Trial Of Naloxegol In
                  Patients With Opioid-Induced Constipation

PR Newswire

SAN FRANCISCO, Feb. 26, 2013

SAN FRANCISCO, Feb. 26, 2013 /PRNewswire/ -- AstraZeneca today announced
high-level results from KODIAC-08, an open-label, randomised, 52-week,
long-term safety trial of naloxegol versus usual care (UC) in patients with
non-cancer related pain and opioid-induced constipation (OIC). UC was defined
as the investigator's choice of an existing laxative treatment regimen for
OIC. This is the fourth trial in the naloxegol Phase III development
programme, and was designed to evaluate the long-term safety and adverse event
(AE) profile of naloxegol in patients taking 25 mg once daily, as compared to

In the trial, a total of 534 patients received naloxegol once daily for up to
52 weeks, while 270 patients received UC for OIC during the same treatment
period. The most commonly reported AEs occurring more frequently on naloxegol
than on usual care included abdominal pain, diarrhoea, nausea and headache.
The trial reported no imbalances in serious adverse events (SAEs). In
addition, there were a low number of major adverse cardiovascular events
(MACE), as adjudicated by an independent external committee, and there was no
imbalance of these events across naloxegol and UC arms.

There were no increases from baseline levels in mean daily pain scores or mean
total daily opioid dose in either the naloxegol or the UC arm. Additionally,
there were no reports of opioid withdrawal AEs which could be attributed to
naloxegol. A full assessment of the safety and tolerability findings is

"These high-level results are similar to the safety results seen in the Phase
III studies previously reported and provide further confidence in the data
we've seen to date for naloxegol," said Briggs Morrison, M.D., Executive Vice
President, Global Medicines Development, AstraZeneca. "We have now completed
our core Phase III programme and we are pleased to advance naloxegol toward a
regulatory submission later this year." A New Drug Application (NDA) filing in
the US and a Marketing Authorisation Application (MAA) filing in the EU are
planned for the third quarter of 2013, pending AstraZeneca's final preparation
of the registration package and a pre-NDA meeting with the FDA.

The core Phase III KODIAC programme for naloxegol is comprised of four
clinical trials, designed to investigate the safety and efficacy of naloxegol
for the treatment of OIC in patients with non-cancer related pain. Three
trials reported high level results in November 2012, including KODIAC-04, -05
and -07. KODIAC-04 and -05 were pivotal 12-week efficacy and safety trials,
while KODIAC-07 was a 12-week safety extension of KODIAC-04.

Full results from KODIAC-04 and -05 will be presented at Digestive Disease
Week (DDW), 18-21 May, 2013. Full results from KODIAC-07, along with
KODIAC-08, will be presented at a scientific meeting later in 2013.

Naloxegol is part of the exclusive worldwide license agreement announced on 21
September 2009, between AstraZeneca and Nektar Therapeutics (NASDAQ: NKTR).

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.

About Naloxegol
Naloxegol is a peripherally-acting mu-opioid receptor antagonist being
investigated for the treatment of constipation 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 receptors in the gastrointestinal tract, constipation
may occur. Opioid-induced constipation 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) of 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.

About Nektar
Nektar Therapeutics 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

About AstraZeneca
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:

SOURCE Nektar Therapeutics

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