Gilead Announces Interim 12-Month Phase III Study Results for Aztreonam Lysine for Inhalation in Patients With Cystic Fibrosis
June 13 2008 - 8:30AM
Business Wire
Gilead Sciences, Inc. (Nasdaq:GILD) today announced results from an
interim analysis of 12-month data from its open-label, Phase III
AIR-CF3 (006) study of aztreonam lysine for inhalation, an
investigational therapy in development for the treatment of people
with cystic fibrosis (CF) who have pulmonary Pseudomonas aeruginosa
(P. aeruginosa). AIR-CF3 is an ongoing, multi-center study designed
to evaluate the safety of repeated exposure to aztreonam lysine in
cystic fibrosis patients who originally participated in the pivotal
Phase III AIR-CF1 (007) or AIR-CF2 (005) studies. These data were
presented by Christopher M. Oermann, MD, Associate Professor of
Pediatrics, Director, Pediatric Pulmonary Fellowship Training
Program, Baylor College of Medicine, at the 31st Annual European
Cystic Fibrosis Conference taking place June 11-14 in Prague, Czech
Republic. �Cystic fibrosis-related pseudomonal infection of the
tracheo-bronchial tree is a chronic condition which, once
established, can be treated but not eliminated. The steadily
increasing life expectancy of CF patients and the chronic nature of
this infection underscore the importance of long-term safety and
efficacy data for potential new respiratory therapies,� said Dr.
Oermann. �Since the usual course of lower respiratory tract
pseudomonal infection is progressive loss of lung function, it is
important that the CF community have long-term data to best
understand the therapeutic profile of treatments for this disease.�
In AIR-CF3, 274 patients received treatment with 75 mg of aztreonam
lysine administered twice-daily or three times daily by the PARI
eFlow� Electronic Nebulizer in accordance with the same regimen
they received in the AIR-CF1 or AIR-CF2 studies. Baseline was
defined as the first visit in the AIR-CF3 study. The mean age of
patients treated with aztreonam lysine in the trial was 28.5 years.
At baseline, the mean overall score on the Respiratory Symptoms
scale of the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a
patient-reported outcome tool, was 61.9 points (on a scale of 0 to
100). The mean percent predicted forced expiratory volume in one
second (FEV1), a standard measure of pulmonary function, was 55.6
percent overall at baseline. Patients will be followed for an
overall treatment period of 18 months. At the time of this
analysis, 64 patients had discontinued treatment. The most common
reasons for discontinuations were personal or administrative
reasons or adverse events. A total of 99 patients have completed
the full 18 months of treatment and the remaining 111 patients
currently receiving aztreonam lysine treatment are expected to
complete the study by the fourth quarter of 2008. Study Results In
this analysis, 120 patients had reached the 12-month, six treatment
course (28 days on and 28 days off) study milestone, with 48
patients in the twice-daily group and 72 patients in the three
times daily group. A compliance rate of 95 percent was observed
over six courses of treatment and no difference in compliance was
observed between the twice-daily and three times daily regimens.
Patients receiving aztreonam lysine three times daily experienced
improvements in FEV1 after completion of six courses of treatment,
with a mean change from baseline of 5.2 percent (SD=18.4; n=70).
These patients also experienced a mean improvement from baseline of
4.2 points in the CFQ-R Respiratory Symptoms scale (SD=20.2; n=70)
after completion of six courses of treatment. Mean values for the
three times daily group did not drop below baseline FEV1 percent
predicted or CFQ-R Respiratory Symptoms scores during any
on-treatment or off-treatment interval over the first 12 months of
treatment. Over six courses of treatment, aztreonam lysine three
times daily was also associated with reductions in P. aeruginosa
colony forming units (a measure of the amount of bacteria present
in the lungs), with a mean change from baseline of -0.42 (log
reduction, SD=2.11; n=52) in the three times daily group. The
incidence of hospitalization for all courses pooled over a period
of up to 18 months (n=274 patients) was 41.2 percent (n=113) and
the median time to hospitalization was 390 days. Aztreonam lysine
was well tolerated with a safety profile consistent with the
expected symptoms of a patient with underlying cystic fibrosis
disease. In an integrated analysis of patients receiving aztreonam
lysine during the placebo-controlled AIR-CF1 and AIR-CF2 studies,
the most common adverse events were cough, nasal congestion,
pyrexia, wheezing, pharyngolaryngeal pain, chest discomfort and
rhinorrhea. No suggestion of increasing incidence of adverse events
was shown over repeated courses of aztreonam lysine. No changes in
pseudomonas sensitivity to aztreonam lysine were observed (as
measured by minimum inhibitory concentrations increased by four
fold in either the MIC50 or MIC90) in the three times daily group.
�Chronic pseudomonal infection represents the single greatest cause
of morbidity and mortality for people with cystic fibrosis,� said
J. Stuart Elborn, MD, FRCP, Professor of Respiratory Medicine at
Queen�s University of Belfast and President of the European Cystic
Fibrosis Society. �Given the�challenges of antibiotic resistance,
there is a need for�a number�of inhaled antibiotics � working
through different mechanisms of action � to treat�pseudomonal
infection in CF.� Aztreonam lysine for inhalation is an
investigational therapy and has not yet been determined safe or
efficacious in humans. About the Aztreonam Lysine Phase III
Clinical Program The Phase III AIR-CF clinical program was designed
to determine the safety and efficacy of aztreonam lysine for
inhalation for use in people with cystic fibrosis who have
pulmonary P. aeruginosa. In each of these studies, aztreonam lysine
for inhalation was administered by the PARI eFlow Electronic
Nebulizer. AIR-CF1 was a randomized, double-blind,
placebo-controlled study designed to assess the safety and efficacy
of a 28-day treatment course of aztreonam lysine in people with CF
who have pulmonary P. aeruginosa. Patients were randomized to
receive 28 days of treatment with 75 mg aztreonam lysine or
volume-matched placebo administered three times daily by the PARI
eFlow Electronic Nebulizer. Patients were followed for an overall
study period of 42 days, with 14 days of observation after
completing aztreonam lysine or placebo therapy. Results from this
study were presented at the North American Cystic Fibrosis
Conference (NACFC) in Anaheim, California on October 4, 2007.
AIR-CF2 was a randomized, double-blind, placebo-controlled study
designed to assess the safety and efficacy of a 28-day treatment
course with aztreonam lysine for inhalation following a 28-day
treatment course of tobramycin inhalation solution in people with
CF who have pulmonary P. aeruginosa. Patients were randomized to
receive 28 days of treatment with 75 mg of aztreonam lysine or
volume-matched placebo each administered twice-daily or three times
daily by the PARI eFlow Electronic Nebulizer. Patients were
followed for an overall study period of 126 days, with 56 days of
observation after receiving aztreonam lysine for inhalation therapy
or placebo. Results from this study were presented at the Cystic
Fibrosis Therapeutics Development Network conference in Seattle,
Washington on April 19, 2007 and at the European Cystic Fibrosis
Conference in Belek, Turkey on June 14, 2007. Gilead also recently
initiated a European Phase III study (0110) comparing aztreonam
lysine for inhalation to inhaled tobramycin. 0110 is an open-label,
multi-center, randomized, parallel group study designed to assess
the comparative safety and efficacy of aztreonam lysine for
inhalation and tobramycin nebulizer solution in adult and pediatric
cystic fibrosis patients with pulmonary P. aeruginosa. The primary
efficacy endpoint is the relative change in FEV1 percent predicted
at Day 28 compared to baseline. The study will enroll approximately
200 patients across Europe. Patients will be randomized to receive
28-day, intermittent, repeating courses of either aztreonam lysine
for inhalation or tobramycin nebulizer solution over a 24-week
treatment period. The total study period will be 26 weeks. About
Aztreonam Lysine for Inhalation Aztreonam lysine for inhalation is
an antibiotic candidate currently being evaluated for people with
cystic fibrosis who have pulmonary P. aeruginosa. Aztreonam has
potent activity against Gram-negative bacteria such as P.
aeruginosa. Aztreonam formulated with arginine is�a U.S. Food and
Drug Administration (FDA)-approved agent for intravenous
administration. Aztreonam lysine is a proprietary formulation of
aztreonam developed specifically for inhalation and has been
designated with orphan drug status in the United States and Europe.
Gilead submitted its U.S. New Drug Application for aztreonam lysine
for inhalation to the FDA on November 16, 2007. The FDA has
established a target review date, under the Prescription Drug User
Fee Act, of September 16, 2008. In Europe, the investigational
product is referred to as aztreonam lysine 75 mg powder for
nebuliser solution. Gilead submitted its Marketing Authorisation
Application (MAA) for marketing approval of aztreonam lysine 75 mg
powder for nebuliser solution (aztreonam lysine) in the European
Union on March 7, 2008. Gilead submitted its application for
aztreonam lysine in Australia on November 30, 2007 and in Canada on
March 21, 2008. About PARI Pharma and the eFlow� Electronic
Nebulizer Aztreonam lysine for inhalation is delivered by the
eFlow� Electronic Nebulizer, developed by PARI Pharma GmbH. eFlow
is a portable nebulizer that enables aerosolization of liquid
medications via a vibrating, perforated membrane. PARI Pharma also
contributed to the development and optimization of the drug
formulation (aztreonam lysine for inhalation) for delivery via
eFlow. Based on PARI�s 100-year history working with aerosols, PARI
Pharma is dedicated to advancing inhalation therapies by developing
innovative delivery platforms and new pharmaceutical formulations
that work together to improve patient care. About Cystic Fibrosis
Today, more than 70,000 people worldwide have cystic fibrosis.
Cystic fibrosis is a chronic, debilitating genetic disease. A major
characteristic of cystic fibrosis is production of abnormally
thick, sticky mucus in the lungs that traps bacteria and
predisposes people with cystic fibrosis to lung infections, which
damage their lungs. Pulmonary infection with Gram-negative
bacteria, particularly pulmonary P. aeruginosa, represents the
single greatest cause of morbidity and mortality among people with
cystic fibrosis. Currently there is no known cure for cystic
fibrosis, and the goal of cystic fibrosis therapy is to control
symptoms and prevent further lung damage. About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers,
develops and commercializes innovative therapeutics in areas of
unmet medical need. The company�s mission is to advance the care of
patients suffering from life-threatening diseases worldwide.
Headquartered in Foster City, California, Gilead has operations in
North America, Europe and Australia. This press release includes
forward-looking statements, within the meaning of the Private
Securities Litigation Reform Act of 1995, that are subject to
risks, uncertainties and other factors, including the risks that
the marketing authorization applications submitted by Gilead for
aztreonam lysine for inhalation for the treatment of cystic
fibrosis in the United States, the European Union, Australia and
Canada may not be granted under the timelines currently
anticipated, or at all. These risks, uncertainties and other
factors could cause actual results to differ materially from those
referred to in the forward-looking statements. The reader is
cautioned not to rely on these forward-looking statements. These
and other risks are described in detail in Gilead's Annual Report
on Form 10-K for the year ended December 31, 2007 and its Quarterly
Reports on Form 10-Q for the first quarter of 2008, as filed with
the U.S. Securities and Exchange Commission. All forward-looking
statements are based on information currently available to Gilead,
and Gilead assumes no obligation to update any such forward-looking
statements. For more information on Gilead, please call the Gilead
Public Affairs Department at 1-800-GILEAD-5 (1-800-445-3235) or
visit www.gilead.com.
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