Pharmacopeia advances dual cardiovascular drug into Phase II

By Mike Nagle

- Last updated on GMT

Pharmacopeia plans to expand the Phase I clinical study of its
cardiovascular drug while beginning the next stage of trials,
following promising results so far.

The US drug company has announced positive Phase I results for its lead drug candidate, PS433540, a Dual Acting Receptor Antagonist (DARA) that combines the blocking effects of two vasodilating drugs to target angiotensin II (AII) and endothelin 1 (ET1) receptors. By blocking both at once, Pharmacopeia hopes its drug will prove superior to either molecule alone at treating hypertension, congestive heart failure and diabetic kidney disease (nephropathy). Diabetic nephropathy represents a large, growing unmet medical need with a high mortality rate, affecting an estimated 8m diabetics in the US, Europe and Japan. During the single ascending dose (SAD) study, no safety or tolerability issues were observed at 20, 50, 100, 250, 500 and 1000 mg. This latest, multiple ascending dose (MAD) trial has so far examined 50, 100, 250, and 500 mg "without significant safety signals [and] so we are investigating 1000 mg,"​ Pharmacopeia CEO, Dr Les Browne told DrugResearcher.com. The molecule is based on two drugs that share a common structural feature: Avapro (irbesartan), a AII receptor blocker that is jointly marketed by Bristol-Myers Squibb (BMS) and Sanofi-aventis; and BMS's endothelin 1 receptor blocker BMS-193884. Pharmacopeia stitched together the active parts of these drugs to form a single molecule that they believe will target both receptors. The approach has been tried in the past by other pharma firms but has met with limited success. Although DARA seems to have a good safety profile, Pharmacopeia is yet to prove its efficacy. "The MAD and SAD studies are safety and tolerability studies and not designed to investigate anticipated pharmacology,"​ said Browne. "We are investigating pharmacology in the AII challenge study that is running and will look at efficacy in the Phase II proof-of-concept study in hypertensive patients." ​ That Phase II study, to establish PS433540's ability to lower blood pressure in hypertensive patients, is already being started and the company hopes to report on the angiotensin challenge study in the next month or so. An endothelin challenge study is expected to start by the end of the year, according to Browne.

Related topics Preclinical Research

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