AstraZeneca Submits For New Dosage Strengths Of Atacand Plus - New Dosing Regimen Offers Patients Greater Chance To Reach Target Blood Pressure

Main Category: Hypertension
Also Included In: Regulatory Affairs / Drug Approvals;  Pharma Industry / Biotech Industry
Article Date: 01 Jul 2008 - 2:00 PDT

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AstraZeneca announced a European decentralized procedure (DCP) submission seeking approval for two new dose strengths of Atacand Plus, for those hypertensive patients not optimally controlled by monotherapy. The reference member state for the procedure is Sweden, and the submission incorporates data from three studies. 1,2,3

The new strengths of the fixed dose combination Atacand Plus, comprised of candesartan cilexetil and hydrochlorothiazide (HCT) in doses of 32/12.5mg or 32/25mg, will offer a second line hypertension indication for hypertensive patients who are not optimally controlled. The clinical studies in this submission show that Atacand Plus at these doses is more effective in reducing blood pressure than their monotherapy components taken alone. In addition, the fixed dose of Atacand Plus 32/25mg was more effective than 32/12.5mg in hypertensive patients who had inadequate blood pressure control with candesartan monotherapy. 1

Hypertension presents an important worldwide public-health challenge because of its prevalence and its associated risks for important cardiovascular and kidney disease.4 Worldwide, 7.6 million premature deaths (about 13.5 per cent of the global total) and about 54 per cent of stroke and 47 per cent of ischaemic heart disease are attributable to high blood pressure. Hypertension is also a major risk factor for chronic heart failure.5

"The new fixed dose combination provide clinicians the opportunity to treat patients, whose blood pressure is not adequately controlled with their current regimen, by a new treatment option that will help to realize greater success in achieving target blood pressure control," commented Professor Bönner, Medical Director of MEDIAN clinics, Bad Krozingen, Germany. "As well as increased efficacy we hope that a once daily tablet will assist with improved patient compliance."

The trials supporting the new doses included a study with an eight-week single-blind run-in phase on candesartan 32mg followed by an eight-week randomised, double-blind phase with three parallel treatment groups (candesartan 32mg, candesartan/HCT 32/12.5mg or candesartan/HCT 32/25mg).1 After a five-week placebo run-in, a second study randomised patients to eight-week double-blind treatment with placebo, HCT 25mg, candesartan 32mg or candesartan/HCT 32/25mg.2 The third study consisted of an eight-week double-blind study of patients randomized to placebo, HCT 12.5 mg, candesartan 32 mg, or the combination of candesartan and HCT. 3

In this program of clinical studies Atacand Plus at these doses was generally well tolerated, and substantial blood pressure reductions were apparent within four weeks of starting treatment with these fixed dose combinations.

About candesartan (Atacand®)

Atacand (candesartan cilexetil) is an angiotensin receptor blocker (ARB), indicated for the treatment of patients with hypertension and patients with CHF and left ventricular systolic dysfunction.

Atacand acts on the renin-angiotensin system (RAS), which plays an important role in regulating blood pressure. Angiotensin II, the main effector hormone in the RAS, mediates a wide range of responses such as vasoconstriction, sodium and fluid retention, cell growth, and sympathetic activation. Atacand binds to the AT1-receptor thereby blocking its interaction with angiotensin II. This blockade leads to vasodilatation and a decrease in blood pressure. Atacand is at least as effective as other antihypertensive drugs but with the advantage of the better tolerability profile associated with ARBs.6

Atacand was first launched for hypertension in 1997 and is currently approved and marketed in over 70 countries around the world. In 2004 Atacand received the first approval for the treatment of CHF in patients with left ventricular systolic dysfunction.

Candesartan cilexetil is marketed by AstraZeneca under trademark Atacand®, Ratacand®, and the fixed dose combination with hydrochlorothiazide is marketed under trademark Atacand Plus, Atacand Plus mite, Atacand Zid, Hytacand, Ratacand Plus and is manufactured under the license from Takeda Pharmaceutical Company Ltd.

About AstraZeneca

AstraZeneca is a major international healthcare business engaged in research, development, manufacturing and marketing of prescription pharmaceuticals and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of US $29.55 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection product sales. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.

References

1. Bönner, G. for the Multicenter Study Group. A combination of high dose candesartan and hydrochlorothiazide is effective and well tolerated in hypertensive patients not controlled on high dose candesartan alone. J Hypertens, 2008;26 Suppl 1:S 467

2. Data on file, AstraZeneca, 2008

3. Papademetriou V, Reif M, Henry D, Neutel JM. Levine JH, Hardison D et al for the Candesartan Cilexetil/Hydrochlorothiazide combination study investigators. Combination therapy with candesartan cilexetil and hydrochlorothiazide in patients with systemic hypertension. J Clin Hypertens 2000;2:372-8.

4. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J; Global burden of hypertension: analysis of worldwide data. Lancet 2005;365:217-23

5. Lawes C, Vander Hoorn S, Rodgers A; For the International Society of Hypertension Global burden of blood-pressure-related disease, 2001 Lancet 2008;371:1513-18

6. Easthope SE, Jarvis B. Candesartan cilexetil. An update of its use in essential hypertension. Drugs 2002;62:1253-87

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