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Munich, March, 28th 2011
PHOENIX Phase III trial of PHP for distributive shock to
continue after positive midpoint recommendation from DMB
The PHOENIX trial is a European, placebocontrolled,
Phase III study treating catecholamine-resistant patients in distributive shock with
the Nitric Oxide (NO) scavenger Pyridoxalated Haemoglobin Polyoxyethylene Conjugate
(PHP). The study was launched by Curacyte AG in Austria, Belgium, Germany, Spain, The
Netherlands and in the United Kingdom in 2009. Today the successful completion of the
second interim analysis on safety and mortality data of 50% of the study population in the
trial is reported. Statistical results were reviewed in an unblinded fashion by an independent
Data Monitoring Board (DMB). The DMB, consisting of intensive care physicians, bioethical
experts and statisticians from the US and Europe came to the conclusion, that the study
should be continued without change.
The continuation of the PHOENIX study represents encouraging news for the management
of critically ill patients suffering from catecholamine-resistant distributive shock for whom
satisfactory treatment options are currently lacking. The trial is designed to statistically
demonstrate survival benefit for patients treated with PHP after 28 days compared to placebo
(+ standard care), and at day 60 and day 90 as secondary endpoints.
In interpretating the DMB’s recommendation, it can be concluded that the overall safety
profile of the company’s lead product PHP appears acceptable without signals or trends
which might require modification or suspension of the trial. Consequently, the pivotal study
will be continued according to the plan with the following key milestones:
To date more than 300 of the 454 target patients have been enrolled in the study. The next
step will be the last interim analysis on 75% of the patients envisaged in Q4/2011 and the
completion of recruitment by the end of 2011. Final top-line results are likely to be available
in Q2 / 2012.
About PHP:
Scientists from Apex Bioscience, Inc. (Chapel Hill, North Carolina), Curacyte’s wholly-owned
US subsidiary, have developed the modified haemoglobin product with the intention to exploit
the natural NO-scavenging and metabolizing properties of haemoglobin. There is compelling
evidence that NO is responsible for vasodilation and hypotension in distributive shock. In the
successfully conducted Phase II clinical development program PHP has previously been
demonstrated to reverse vasodilation and resolve hypotension associated with this form of
shock.
About the PHOENIX trial:
This Phase III, multi-center, randomized, placebo-controlled study compares the
effectiveness of continuous infusion of PHP plus conventional vasopressor therapy against
placebo (normal saline) plus conventional vasopressor therapy in patients with
catecholamine-resistant distributive shock. In addition, the safety and tolerability of this new
treatment modality will be evaluated.
For inclusion into the trial the patients must be adequately resuscitated with fluids and must
require a norepinephrine dose of .0.3 mcg/kg/min to maintain a mean arterial blood pressure
of . 65 mmHg. Furthermore, patients must at least fulfill two criteria indicative of a systemic
inflammatory response ("SIRS" criteria). PHP as active compound or placebo will be
administered by continuous intravenous infusion at 0.25 ml/kg/hr for a maximum of 150
hours.
Efficacy will be demonstrated by PHP significantly reducing 28-day all-cause mortality.
Secondary endpoints will include: Survival time, survivor days in the intensive care unit
("ICU") and time on mechanical ventilation and on vasopressors.
The trial is being conducted in 72 hospitals in six European countries and led by Prof. Jean-
Louis Vincent from the Erasme University in Brussels as the coordinating principal
investigator in Europe.
About Curacyte:
Curacyte AG is an advanced biopharmaceutical company dedicated to the development of
new therapeutics for acute and critical care. After sale of its preclinical technology platform
for low molecular weight protease inhibitors to The Medicines Company in 2008, Curacyte
has focussed all its efforts on the development of PHP.
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