Friday, March 11, 2005

NOVARTIS' ALISKIREN SHOWN TO BE SAFE, EFFECTIVE IN LOWERING BLOOD PRESSURE, RESEARCHERS REPORT

Novartis AG's investigational drug, Aliskiren (SPP100), a renin inhibitor, safely and effectively lowers blood pressure (BP) in patients with mild to moderate hypertension, findings from a new study suggest.

"Because renin catalyzes the first and rate-limiting step of the RAS [renin-angiotensin system] and has high specificity for its substrate, angiotensinogen, renin inhibitors offer the potential for blocking this complex hormonal system at its initial point of activation, with a low likelihood of side effects," wrote investigators.

According to the authors, Aliskiren is the first in a new class of orally effective, nonpeptide, low-molecular-weight renin inhibitors.

In a recent study of patients with mild to moderate hypertension, a 300 mg/day dose of Aliskiren was shown to lower BP with efficacy and tolerability similar to Merck & Co. Inc.'s Cozaar (losartan potassium) at twice the recommended daily dose.

To further explore the efficacy and safety of Aliskiren, the researchers conducted a separate randomized, double-blind trial that enrolled 652 patients with mild to moderate hypertension (mean sitting diastolic blood pressure [DBP] of at least 95 mm Hg but less than 110 mm Hg). After a two- to four-week placebo run-in period, participants were assigned to receive 150 mg, 300 mg or 600 mg of Aliskiren, 150 mg of irbesartan (an angiotensin receptor blocker) or placebo once daily for eight weeks.

Results showed all three doses of Aliskiren significantly reduced both trough mean sitting DBP and systolic blood pressure (SBP) as compared with placebo. Least-squares mean reductions in trough DBP were 9.3 mm Hg with Aliskiren 150 mg/d, 11.8 mm Hg with 300 mg/d and 11.5 mm Hg with 600 mg/d compared with 6.3 mm Hg with placebo. Least-squares mean reductions in trough SBP with Aliskiren were 11.4 mm Hg, 15.8 mm Hg and 15.7 mm Hg, respectively, compared with 5.3 mm Hg with placebo.

Least-squares reductions in mean sitting DBP and SBP with irbesartan were 8.9 mm Hg and 12.5 mm Hg, respectively. The reductions in sitting DBP with Aliskiren 300 mg and 600 mg were significantly greater than that seen with irbesartan.

The incidence of adverse events and the number of patients discontinuing therapy with Aliskiren were similar to results seen in patients receiving placebo or irbesartan. The most common adverse effects reported were headache, dizziness and diarrhea.

"Given the success of ACE inhibitors and AT1-receptor blockers in reducing morbidity and mortality across a broad range of disease states, it seems reasonable to speculate that renin inhibitors such as Aliskiren may provide such benefits," the authors wrote.

"Whether these benefits are equal to, greater than or less than those seen with existing RAS inhibitors will require long-term endpoint assessment studies. Aliskiren nevertheless offers the prospect of highly effective RAS inhibition for the treatment of hypertension and related cardiovascular diseases using a new pharmacological approach," they added.

Joerg Reinhardt, head of development at Novartis Pharma AG, said that with Aliskiren's unique effect on renin, the drug may "offer further protection for the heart and kidney as well."

Irbesartan is marketed by Bristol-Myers Squibb Co. and Sanofi-Synthelabo SA as Avapro and as Avalide when combined with hydrochlorothiazide.

Results of the study were published in the March issue of the journal Circulation.