New fixed-dose combination therapy option offers potent blood pressure reduction and tolerability profile similar to placebo: 

 Sanofi announced today that the European Commission has approved irbesartan-hydrochlorothiazide (HCTZ) for second-line treatment of hypertension. The fixed-dose combination product, which will be marketed in Europe under the brand name COAPROVELÔ , combines two hypertensive therapies, irbesartan (APROVEL® ) and a low dose of hydrochlorothiazide, in two fixed-dose formulations, 150 mg irbesartan/ 12.5 mg HCTZ tablets, and 300 mg irbesartan/ 12.5 mg HCTZ tablets.

 Treatment with combination therapy is often recommended when the response to antihypertensive monotherapy is sub-optimal. Irbesartan, a compound from Sanofi Research, is a highly effective once-a-day angiotensin II receptor antagonist (AIIRA) that specifically blocks the cardiovascular effects of angiotensin II, dilating blood vessels and lowering blood pressure.

 lrbesartan has now been combined with the anti-hypertensive hydrochlorothiazide (HCTZ), a diuretic that lowers blood pressure by increasing the excretion via the kidneys of sodium and chloride. HCTZ is commonly prescribed in combination with other blood pressure lowering therapies and is particularly effective in combination with RAS-type agents like AIIRAs.

 In two randomized well controlled clinical trials, irbesartan as a monotherapy demonstrated superior reductions in blood pressure to losartan. Additionally, one of these studies further demonstrated that the regimen of irbesartan combined with HCTZ was superior to the losartan and HCTZ regimen. And now for the first time, the European Commission has approved two fixed-dose combinations of the same AIIRA, irbesartan, further extending these blood pressure lowering benefits to a broader range of hypertensive patients.

 The European approval is based upon controlled clinical trials involving over 2,700 hypertensive patients worldwide. Up to 90% of hypertensive patients (either diastolic blood pressure below 90mm Hg or l0 mm reduction in DBP) responded to irbesartan/HCTZ-based regimens over a 12-month period. Normalization rates (diastolic blood pressure below 90mm Hg) were as high as 83%. Additionally, the incidence of side effects was similar to placebo for the irbesartan/HCTZ combination doses up to 300 mg irbesartan and 12.5 mg HCTZ and the discontinuation rate due to adverse events for irbesartan/HCTZ was 3.6 % versus 6.8% for placebo.

 "The entry of the irbesartan combination in the antihypertensive marketplace provides physicians with a very effective option for a broader spectrum of patient types", said Bernard Waeber, M.D., Professor of Medicine (Division of Hypertension and Vascular Medicine) ; Centre Hospitalier Universitaire Vaudois ; Lausanne, Switzerland, "and this combination offers something unique; a highly effective AIIRA combined with a low dose of HCTZ that provides potent blood pressure response with an excellent tolerability profile."

 Extensively studied in clinical trials in more than 7,500 patients, irbesartan received marketing clearance in Europe in September, 1997 as a first-line treatment for hypertension and is marketed by Sanofi and Bristol-Myers Squibb in over 25 markets worldwide under the APROVEL® /KARVEA® /AVAPRO® brand names.

 The co-development and marketing agreement between Sanofi and Bristol-Myers Squibb initiated in 1993 involves two compounds from Sanofi Research, clopidogrel and irbesartan. The clinical development of clopidogrel was conducted under the leadership of Sanofi and that of irbesartan under the leadership of Bristol-Myers Squibb. Both compounds are marketed worldwide by Sanofi and Bristol-Myers Squibb.

 With marketing approval for COAPROVELÔ and its excellent profile, Sanofi today sees further results of its sustained R&D efforts.

Press Contacts

Thierry Orsoni: (33) 1.53.77.41.08

Investor Relations Contacts

In Paris : (33) 1.47.44.24.63
In New York : (1) 212.922.3004