Enoximone

On March 25, 2004 Myogen Inc. announced preliminary results from its Phase III clinical trial of enoximone capsules. The 201 participants were patients with the most advanced stages of chronic heart failure who were dependent on intravenous (IV) inotrope therapy. The study was designed to evaluate enoximone capsules as an effective treatment to wean patients off of IV inotrope therapy and potentially support the two ongoing Phase III pivotal studies, ESSENTIAL I & II. Analysis of the primary endpoint, wean success at 30 days, demonstrated a wean success rate of 61% in the enoximone-treated group and 51% in the placebo-treated group. This difference did not reach statistical significance (p = 0.171).

Enoximone is a small organic molecule that selectively inhibits type-III phosphodiesterase (PDE-III). PDE-III is an enzyme that is present in the heart and plays an important regulatory role in cardiac function. PDE-III inhibitors block the action of this enzyme, increasing the force of contraction of the heart and increasing the rate of relaxation, thereby increasing cardiac output. Enoximone also causes vasodilation, an increase in the diameter of blood vessels, through its effects on smooth muscle cells that surround blood vessels, which results in lower pressure against which the heart must pump. Positive inotropy and vasodilation can both be therapeutically useful in the treatment of heart failure.

Chronic heart failure (CHF) generally occurs in patients with a long history of uncontrolled high blood pressure or in patients that have suffered a heart attack or some other heart-damaging event. It is estimated that half of all patients with this disorder die within five years of diagnosis. CHF therapeutics are a $14 billion market that is expected to grow to more than $22 billion in 2008.

The failure of enoximone to achieve statistical significance at the primary endpoint in this clinical trial is important. However, Myogen’s pivotal clinical trials with oral enoximone, ESSENTIAL I & II, are expected to complete their treatment phase by the end of 2004. Until these clinical trial results are released and analyzed, Biohorizon recommends no preliminary assessment activities.

Technology Details
Target Disease / Indication
Chronic Heart Failure (CHF)

Technology Classification
Drug

Body System
Cardiovascular System

Program Area
Medicine/Cardiology

Regulatory Status
Phase III

BioHorizon Impact Score
67/100 – High