Subject:
Alliance Pharmaceutical Corp. Press Release
Date:
Mon, 10 Aug 1998 17:51:41 -0700
From:
Gwen Rosenberg <owner-owner@allp.com>
Reply-To:
Gwen Rosenberg <GHR@allp.com>
August 10, 1998
LiquiVent(R) Update...
The following is a summary of recent progress with LiquiVent(R),
Alliance's "liquid ventilation" drug for treatment of acute lung injury
and acute respiratory distress syndrome (ARDS). LiquiVent is an
oxygen-carrying liquid (perflubron) administered directly into the lungs
of a patient who is being supported by a mechanical ventilator. The
goal of LiquiVent therapy is to facilitate the exchange of respiratory
gases while protecting the lungs by reducing the patient's exposure to
the harmful effects of conventional mechanical ventilation. LiquiVent
is being evaluated for use with adult, pediatric, and infant patients,
and it is being developed and reviewed under U.S. Food and Drug
Administration (FDA) "fast track" regulations.
ADULT PROGRAM
Previous Phase II Adult Study
As reported earlier, Alliance had previously completed a Phase II study
with adult patients. This study demonstrated a significant improvement
in "ventilator-free days" and a trend in improved mortality for a subset
of patients who received LiquiVent, compared to patients who were
treated with conventional mechanical ventilation.
New Clinical Data
Alliance recently completed a small, multicenter Phase II study with
adult patients. The purpose of the study was to validate the protocol
for a subsequent adult pivotal trial. Patients were treated for up to
five days according to Alliance's proprietary partial liquid
ventilation(SM) technique, and they received either a "full" dose
(approximately 100% of functional residual capacity) or a "half" dose
(approximately 50% of functional residual capacity) of LiquiVent.
Patient Population - The study was open to male and
female patients between the ages of 16 and 65 who had been diagnosed
with ARDS (according to the definition determined by the 1994 conference
report from The American-European Consensus Conference on ARDS), plus a
PEEP of 8cm H2O. Special efforts were used to select patients at the
most seriously ill end of the ARDS spectrum, for whom LiquiVent
potentially offers its greatest benefit. Sixteen patients were enrolled
in the study. Their ARDS conditions were due to sepsis, pneumonia,
trauma, aspiration of gastric contents, or other causes.
Results - Detailed data from the study will be presented
at an upcoming scientific conference. Preliminary results are as
follows:
(a) Mortality - All patients in the study were
treated with LiquiVent (receiving either the "full" or "half" dose).
Mortality at 28 days after initiation of treatment (a standard time
period used to evaluate new therapies) was 6%, and overall mortality to
date was 18%. These results compare favorably with published mortality
rates of 40-50% for conventionally treated ARDS patients.(1,2)
1-Critical Care Medicine, 1998, Vol.26,
No. 1, p.15
2-The New England Journal of Medicine,
1998, Vol.338, No.6, p.355
(b) Safety - The safety data were consistent with
previous reports that LiquiVent treatment is safe for this patient
population. There are no safety concerns regarding the use of LiquiVent
in additional studies with this patient population.
(c) Patient Selection - The results of the study
confirmed the appropriateness of the inclusion/exclusion criteria used
to select the patients.
(d) Ventilator Management - All medical centers
involved with the study used the same algorithms to standardize
ventilator management for all patients. This is an important
accomplishment because ventilator settings and adjustments are typically
somewhat subjective and variable, which can make comparisons between
patients difficult.
(e) Ventilator Weaning - "Weaning" of patients from
the ventilator was also standardized among all of the clinical sites
according to a specified algorithm.
(f) Dose Management - Preclinical data have
indicated that a "half" dose of LiquiVent could provide medically
satisfactory oxygenation. The current study is the first human trial in
which patients have been treated with the lower dose. The study
demonstrated that it is possible to maintain a consistent, low level of
LiquiVent in the patients throughout the course of treatment. This will
allow Alliance to evaluate the benefits of the lower dose compared to
the "full" dose in our planned pivotal trial.
(g) Patient's Experience - Lakeland Regional Medical
Center in Florida, one of the clinical sites participating in the study,
held a press conference on July 20 to discuss the experience of one of
their patients who was treated with LiquiVent. Michael Ebright was
seriously injured in a car accident on July 2, and later developed
respiratory failure due to ARDS. After receiving liquid ventilation
treatment for five days, he was successfully weaned from the ventilator
and moved from the intensive care unit to a regular hospital room. Mr.
Ebright, who spoke with the media accompanied by his wife and small son,
expects to go home as soon as he recuperates from his other injuries.
His story was reported by a number of local television news programs and
newspapers.
Upcoming Phase II/III Pivotal Study
Based on the results of the two Phase II studies, Alliance intends to
initiate a pivotal Phase II/III study with adult patients by yearend.
This is expected to be a controlled, multicenter study involving
approximately 400 patients in the U.S., Canada, and Europe. The study
will use the same entry criteria, ventilatory settings, and other
parameters as the recently completed Phase II study. Both doses of
LiquiVent will be evaluated during the initial portion of the study in
order to select the optimal dosing regimen. The study will also compare
the efficacy of liquid ventilation to conventional mechanical
ventilation.
There are approximately 800,000 patients in U.S. intensive care units
who receive at least 24 hours of conventional mechanical ventilation
each year. Adults represent approximately 80-90% of these patients.
PEDIATRIC PROGRAM
Alliance plans to initiate a Phase II LiquiVent study with pediatric
patients this year. This multicenter pilot study will investigate the
use of LiquiVent in conjunction with high-frequency oscillatory
ventilation (HFOV), a new ventilatory method approved for treatment of
infants and children with acute lung injury. Encouraging preclinical
data have been generated using LiquiVent in combination with HFOV.
The primary objective will be to evaluate the safety and feasibility of
treatment with LiquiVent during high-frequency oscillation in pediatric
patients with acute respiratory failure. The study will explore the
hypothesis that LiquiVent administered at a low dose may recruit (open)
collapsed areas of the lung and increase lung volume (as reflected by
improved oxygenation or lung volume measurements), thereby allowing
effective gas exchange in injured lungs where conventional methods of
recruitment have failed.
INFANT PROGRAM
Alliance is also planning a small Phase II infant study with LiquiVent.
This study will include term and near-term infants diagnosed with an
acute onset of severe diffuse lung disease within the first seven days
of life. Patients will receive LiquiVent with or without alternative
pulmonary therapies (extracorporeal membrane oxygenation, high-frequency
oscillatory ventilation, nitric oxide, and pulmonary surfactant). The
LiquiVent-treated infants will be compared to patients receiving
conventional mechanical ventilation or other standard treatments in
order to test key study design features and to collect pilot data for
the design of a larger-scale Phase II study. The primary goals of
liquid ventilation with term infants are to improve pulmonary function
and to reduce the number of days that the patient is on the ventilator.
***
Thank you for your interest in LiquiVent and Alliance Pharmaceutical
Corp. A new LiquiVent Product Fact Sheet is currently under
construction and will be available shortly on our web page. We will let
you know when the Fact Sheet is completed. If you have any questions or
would like additional information, please contact me by e-mail at
mailto:ghr@allp.com, telephone at (619) 558-4375, or fax at (619)
678-4133.
Sincerely,
Gwen Rosenberg
Vice President, Corporate Communications
Except for historical information, the matters set forth in this release
are forward-looking statements that are subject to risks and
uncertainties that could cause actual results to differ materially from
those set forth herein, including the uncertainties associated with the
conduct of preclinical or clinical studies and the timing or ability to
investigate scientific data. Alliance refers you to cautionary
information contained in documents the Company files with the Securities
and Exchange Commission from time to time, including the last Form 10-K
and Form 10-Q, and those risk factors set forth in the recent
registration statement on Form S-3 (Registration Number 333-15905). |
