Single-molecule agent lowered BP in stage I and II hypertension

Phase-2b trial: PS433540 lowered systolic, diastolic BP in dose-dependent fashion compared with irbesartan and placebo.

American Society of Hypertension 24th Annual Scientific Meeting

A novel endothelin and angiotensin I receptor antagonist — DARA — showed promising results in a phase-2b trial presented at the recent American Society of Hypertension Annual Meeting.

Two hundred sixty-one patients with BP between 140/90 mm Hg and 179/109 mm Hg were treated for four weeks with a placebo. They were then randomly assigned to a 12-week treatment period to either placebo (n=59); the dual angiotensin and endothelin-receptor antagonist PS33540 (Ligand Pharmaceuticals) at 200 mg (n=58), 400 mg (n=58) or 800 mg (n=28); or to 300 mg of irbesartan (n=58) (Avapro, Bristol-Myers Squibb Sanofi-Synthelabo).

Researchers assessed primary efficacy endpoints of seated systolic BP, diastolic BP, and percentage of patients who achieved BP control (<140/90 mm Hg).

Joel M. Neutel, MD, said that 9.3% of patients assigned placebo (P<.01 for overall comparison to DARA) and 31.5% assigned irbesartan achieved the BP goal (P<.05 for overall comparison to DARA). That compared with 36.2% of patients assigned 200 mg PS433540, 51.9% assigned 400 mg, and 61.5% assigned 800 mg.

First-in-class compound

Patients assigned the novel DARA at any dose had statistically greater decreases in systolic and diastolic BP (P<.001) and more BP control (P<.0013) compared with patients assigned placebo. Although no severe adverse events were reported, there were 34 mild-to-moderate adverse events in the placebo group, 28 in the irbesartan group, compared with 20 in the 200-mg DARA group, 27 in the 400-mg group and 17 in the 800-mg group.

“This is an interesting first-in-class compound that decreases systolic and diastolic BP very effectively, similar to what you might see with combination therapy in patients with stage I and stage II hypertension, in a dose-dependent fashion,” said Neutel, associate professor of medicine at the University of California Irvine.

“This is an exciting and novel agent that may just give us something new to add to the armamentarium for the management of all hypertensive patients and also patients with resistant hypertension.”

The results of the phase-2a study, designed to evaluate initial tolerability and 24-hour efficacy of the DARA agent in 91 patients with hypertension, were reported at the 2008 American Society of Hypertension Annual Scientific Meeting in New Orleans. – by Eric Raible

For more information:

Neutel J. #LB-OR-02. Presented at: American Society of Hypertension 24th Annual Scientific Meeting; May 6-9, 2009; San Francisco.