Pharmacopeia Announces Positive Data on DARA Drug Candidate

Pharmacopeia has announced positive results from the initial Phase I clinical trial of PS433540, the company's lead internal product candidate for the treatment of hypertension and diabetic nephropathy.

Data from the single-ascending-dose study indicated that PS433540 was well-tolerated at all six doses administered. In addition, study findings suggested that the compound possesses linear pharmacokinetics and a half-life that is consistent with once-daily administration.

PS433540 is the first and only dual-acting angiotensin and endothelin receptor antagonist (DARA) in development. The compound, which possesses two clinically validated mechanisms of action in a single molecule, works by selectively blocking the action of two potent vasoconstrictor and mitogenic agents, angiotensin II (AII) and endothelin 1 (ET1), at their respective receptors.

PS433540 is highly selective for the AII receptor subtype 1 and the ET receptor subtype A. As such, PS433540 combines the properties of an angiotensin receptor blocker and an endothelin receptor antagonist in the same molecule. Preclinical data suggests that, compared with either mechanism alone, simultaneously blocking the actions of both AII and ET1 may provide improved treatment options for several cardiovascular diseases.

The objective of this randomized, placebo-controlled, dose-escalation study was to evaluate the compound's preliminary safety and tolerability by treating six separate groups of healthy volunteers. Each group consisted of eight subjects, with six individuals receiving the active DARA compound and two receiving placebo. PS433540 doses administered to the study groups ranged from 20 to 1,000 mg and were increased for each successive group. In addition to safety and tolerability, dose-related pharmacokinetics were also evaluated.

Phamacopeia's Phase I program for PS433540 consists of multiple studies. Other planned studies include a multiple-ascending-dose study to further evaluate safety after repeated administration of PS433540 over 14 days, as well as an angiotensin challenge study and an endothelin challenge study to demonstrate PS433540's dual pharmacology. Pharmacopeia expects the entire Phase I program to be complete in late 2007, with a Phase II trial beginning in the first half of 2008.