Data published in the March issue of the journal Circulation indicates a significant dose-dependent response with the antihypertensive agent Aliskiren vs. placebo and another antihypertensive, irbesartan. Aliskiren (SPP100) is potentially the first in a new class of orally active renin inhibitors in development for treating hypertension with the potential for improved end organ protection.
"These data support results from earlier studies and provide additional evidence regarding Aliskiren's potential as a useful antihypertensive agent for people with mild-to-moderate hypertension," said lead investigator Alan Gradman, MD, Chief, Division of Cardiovascular Diseases, The Western Pennsylvania Hospital, Pittsburgh, Penn.
In the eight-week study investigators compared the antihypertensive efficacy and safety of Aliskiren with an active comparator, the angiotensin receptor II blocker irbesartan and placebo. Six hundred and fifty-two patients with mild-to-moderate hypertension (mean sitting diastolic blood pressure =95 and <110 mm Hg) were randomized to oral once-daily Aliskiren at 150, 300, or 600 mg doses, irbesartan 150 mg or placebo. All doses of Aliskiren effectively lowered trough (level before next dose is administered) mean sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP). DBP reductions for Aliskiren 150 mg, 300 mg, 600 mg were 9.3mm, 11.8mm, and 11.5mm Hg respectively while SBP reductions were 11.4mm, 15.8mm, and 15.7mm respectively. As with other Aliskiren trials, this study demonstrated dose-dependent efficacy up to the 300 mg dose of Aliskiren.
Joerg Reinhardt, Head of Development, Novartis Pharma AG, says, "People with cardiovascular disease/hypertension are still not being adequately treated to prevent detrimental outcomes. With its unique effect on renin, Aliskiren may offer a new treatment option that goes beyond blood pressure lowering and that will potentially offer further protection for the heart and kidney as well. We continue to be encouraged and look forward to exploring the full potential of the agent."
Suppression of the renin angiotensin system (RAS) using angiotensin converting enzyme inhibitors and angiotensin II receptor blockers has been widely shown to treat hypertension and reduce cardiovascular events.
Aliskiren's novel mechanism of action offers a new way to address the RAS by inhibiting renin and reducing plasma renin activity (PRA), thereby optimizing RAS suppression. Other therapies which act on the RAS provide incomplete suppression due to indirect pathways and compensatory feedback mechanisms which in turn result in increased PRA.
The phase III clinical trial programme for Aliskiren as monotherapy and in combination with other antihypertensive therapies is ongoing. The development of Aliskiren is driven by Novartis' cardiovascular and metabolic research and development programme.
Novartis discovered Aliskiren and licensed it to Speedel, a privately-held biopharmaceutical company in 2000. After completion of phase I and II trials by Speedel, Novartis exercised a call-back option in 2002 and is now solely responsible for development and commercialization of Aliskiren.