Renin inhibitor shows promise in trial

Swiss drugmaker Novartis says that its renin inhibitor drug
aliskiren (SPP100), which potentially represents the first in a new
class of orally-active drugs for high blood pressure, has shown
promising data in a clinical trial.

Asliskiren demonstrated a significant dose-dependent response in a study comparing it to Sanofi-Aventis' already-marketed Aprovel (irbesartan), in the widely-used angiotensin II receptor antagonist class, or placebo.

Renin inhibitors have been pursued as potential new cardiovascular medications since the early-1980s, but to date no drug acting by this mechanism has reached the market. Some researchers consider them as a 'holy grail' of antihypertensive therapy, because of the way they interact with the renin-angiotensin system (RAS) that governs blood pressure.

Aliskiren offers a new way to tackle the RAS by inhibiting renin and reducing plasma renin activity, which optimises RAS suppression, according to Novartis. Other current therapies which act on the RAS, including the AIIRAs and ACE inhibitors, provide incomplete suppression due to indirect pathways and compensatory feedback mechanisms which, in turn, result in increased plasma rennin activity, Novartis noted.

In the eight-week trial, 652 patients with mild-to-moderate hypertension were randomised to receive oral once-daily aliskiren at 150mg, 300mg or 600mg doses, irbesartan 150mg or placebo.

It was found that all doses of aliskiren tested effectively lowered diastolic and systolic blood pressure. This further supports the earlier finding of dose-dependent efficacy up to 300mg. The 150mg dose was equivalent to irbesartan in its ability to lower blood pressure, while at higher doses aliskiren was significantly more effective in reducing diastolic blood pressure.

Joerg Reinhardt, head of development at the Swiss firm, noted: "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 kidneys as well."​ Aliskiren is currently in Phase III trials, both as a monotherapy and in combination with other antihypertensive drugs.

The results are published in the March issue of the journal Circulation.

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