AstraZeneca Announces New Safety Data For Naloxegol In Patients with Opioid-Induced Constipation

  AstraZeneca Announces New Safety Data For Naloxegol In Patients with
  Opioid-Induced Constipation

ACG 2013 Annual Scientific Meeting

Business Wire

SAN DIEGO -- October 14, 2013

AstraZeneca (NYSE: AZN) today announced the results of a Phase III long-term
safety and tolerability study of the once-daily 25mg dose of naloxegol, in
patients with non-cancer pain and opioid-induced constipation (OIC). Naloxegol
is an investigational peripherally-acting mu-opioid receptor antagonist
(PAMORA), which has been studied in OIC in adult patients with chronic
non-cancer pain, a common condition caused by prescription opioid pain
medicines. Data were presented at the American College of Gastroenterology
(ACG) 2013 Annual Scientific Meeting in San Diego, California.

The Phase III study, KODIAC-08 (n=844), was a 52-week, long-term safety trial
of naloxegol (n=534) vs. usual care (n=270) in patients with non-cancer
related pain and OIC. Usual care was defined as the investigator’s choice of
an existing laxative treatment regimen for OIC.

“The data from the long-term safety study further support the safety and
tolerability of naloxegol, a PAMORA which could help address an unmet need for
millions of patients with OIC.” said Kathleen Cantagallo, Clinical VP,
naloxegol, AstraZeneca.

Data from KODIAC-08 reinforces the safety and tolerability findings from
previous Phase III studies, KODIAC-04 and -05. Data from KODIAC-08 included:

  *Most naloxegol-emergent gastrointestinal adverse events (AEs) occurred
    early in treatment and were transient with 9 patients (1.6%) discontinuing
    naloxegol due to abdominal pain;
  *Most common treatment-emergent AEs occurring more often with naloxegol vs.
    usual care were abdominal pain (17.8% vs. 3.3%), diarrhoea (12.9% vs.
    5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 4.8%), and flatulence
    (6.9% vs. 1.1%);
  *There were no imbalances seen in the independently adjudicated
    cardiovascular events between the two groups - 2 patients in each arm of
    the study had major adverse cardiovascular events (MACE) and these events
    were not attributed to study drug;
  *There were two opioid withdrawal AEs reported in patients taking naloxegol
    (both were attributed to decreases or discontinuation of opioid medication
    and both were deemed unrelated to treatment with naloxegol);
  *Pain scores and opioid doses were comparable between treatment groups and
    were stable throughout the study;
  *No bowel perforations occurred in either group of the study.

In addition to the new safety data for naloxegol presented at the 2013
American College of Gastroenterology (ACG) Meeting, there are two additional
data presentations for naloxegol at the meeting:

  *Tuesday, October 15, Plenary Session 2: Endoscopy/Functional Bowel
    Disorders; Chey et. al. “Naloxegol Symptom Responder Rates in Patients
    Opioid-Induced Constipation: Results From 2 Prospective Randomized
    Controlled Trials”
  *Tuesday, October 15, Poster Session: “Chey et. al., “Efficacy of Naloxegol
    in a Subpopulation of Patients With Opioid-Induced Constipation and an
    Inadequate Baseline Response to Laxatives: Results From 2 Prospective,
    Randomized, Controlled Trials”


About Naloxegol

Naloxegol is an investigational peripherally-acting mu-opioid receptor
antagonist (PAMORA), which has been specifically designed for the treatment of
opioid-induced constipation (OIC), a condition caused by prescription opioid
pain medicines. Naloxegol is a once-daily tablet designed to block the binding
of opioids to the opioid receptors in the gastrointestinal (GI) tract without
impacting the opioid receptors in the brain.

Naloxegol is part of the exclusive worldwide license agreement announced on 21
September 2009, between AstraZeneca and Nektar Therapeutics (NASDAQ:NKTR).
Naloxegol was developed using Nektar’s oral small molecule polymer conjugate

About Opioid-Induced Constipation

Opioids bind to specific proteins called opioid receptors. When the opioids
bind to certain opioid receptors in the gastrointestinal (GI) tract,
constipation may occur. Opioid-induced constipation (OIC) is a result of
increased fluid absorption and lower GI motility due to opioid receptor
binding in the GI tract.

Globally, approximately 40–50% (28-35 million) of patients taking opioids for
long-term pain develop OIC. 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 AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialisation of prescription
medicines, primarily for the treatment of cardiovascular, metabolic,
respiratory, inflammation, autoimmune, oncology, infection and neuroscience
diseases. AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more information
please visit:

2919400 Last Updated 10/13


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