Pharmacopeia Confirms Blockade of Angiotensin II Response with First-In-Class PS433540 (DARA)
Results Demonstrate DARA's Potential as Treatment for Hypertension
PRINCETON, N.J., Sept. 27 /PRNewswire-FirstCall/ -- Pharmacopeia (Nasdaq: PCOP), an innovator in the discovery and development of novel small molecule therapeutics, today announced confirmation of the ability of PS433540 (DARA) to block the angiotensin II (AII) response in a Phase 1 trial in healthy volunteers. Numerous similar studies with other agents that block the renin-angiotensin system support that this result is a strong indication that PS433540 can be expected to lower blood pressure in hypertensive patients. The study showed that all doses of PS433540 compared with placebo produced a statistically significant (p<0.01) inhibition of the expected AII-induced increase in blood pressure. Additionally, the findings showed that the 250 mg and 500 mg doses of PS433540 were at least as effective in blocking the AII response as irbesartan, a leading angiotensin receptor blocker for the treatment of hypertension. Furthermore, support for once-a-day oral dosing was provided by PS433540's ability in this study to block the angiotensin II induced blood pressure increase for 24 hours.
'The AII challenge study has been frequently used to confirm the pharmacology and establish the dose for Phase 2 evaluation of compounds that block the renin-angiotensin system,' said Les Browne, Ph.D., President and Chief Executive Officer of Pharmacopeia. 'These positive findings are exciting as they give us further confidence in the DARA concept at a relatively early stage of clinical development.'
This AII challenge study was a double-blind evaluation of placebo and four dose levels of PS433540 (20, 100, 250 and 500 mg) and open label 300 mg of irbesartan in healthy male volunteers. Seventeen subjects received each of the six treatments once, at weekly intervals. At baseline and 2, 4, 12 and 24 hours post-dose, subjects received a six-minute infusion of AII and had their blood pressure measured.
'These encouraging results combined with the positive safety and tolerability data that we have collected from our single and multiple ascending dose studies of PS433540 paint a compelling picture of DARA as a potentially valuable new therapeutic option,' stated Rene Belder, M.D., Pharmacopeia's Vice President of Clinical and Regulatory Affairs. 'We look forward to completing our recently initiated Phase 2a trial of DARA with the hope that the findings of this AII challenge study will be confirmed in hypertensive patients.'
PS433540 is a dual-acting angiotensin and endothelin receptor antagonist (DARA) that is being developed as a potential treatment for hypertension and diabetic nephropathy. PS433540, the first and only DARA compound in development, possesses two clinically proven mechanisms of action in a single compound. The compound works by selectively blocking the action of two potent vasoconstrictor and mitogenic agents, angiotensin II (AII) and endothelin 1 (ET1), at their respective receptors. Preclinical studies have shown that PS433540 is highly selective for the AII receptor sub-type 1 and the ET receptor sub-type A. As such PS433540 combines the properties of an angiotensin receptor blocker (ARB) and an endothelin receptor antagonist (ERA) in the same molecule. There are considerable preclinical and initial clinical data suggesting that compared to either agent alone, simultaneously blocking the actions of both AII and ET1 may provide significantly improved treatment options for several cardiovascular diseases.
surf's up......crikey
