FDA approves New Single-Pill Combination of valsartan and aliskiren to Treat High Blood Pressure

The US Food and Drug Administration (FDA) has approved a new single-pill combination of aliskiren and valsartan tablets (Valturna; Novartis AG, Basel, Switzerland), the first and only medicine to target two key points within the renin system, also known as the renin angiotensin aldosterone system or RAAS, an important regulator of blood pressure.

This is the first approval for the single-pill combination of aliskiren and valsartan, which is indicated for the treatment of high blood pressure in patients not adequately controlled on aliskiren or angiotensin receptor blocker (ARB) monotherapy and as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals.

"This unique combination brings together the powerful blood pressure lowering effects of valsartan and aliskiren," said Joe Jimenez, CEO of the Novartis Pharmaceuticals Division. "It offers an important additional treatment option for physicians and hypertension patients, many of whom are not at their blood pressure goal. Valturna builds upon our strong cardiovascular franchise and is consistent with our long-term commitment to developing effective and innovative therapies. It further strengthens our growing portfolio of single-pill combinations to treat high blood pressure."

The new single-pill combines in a single pill valsartan, the active ingredient in Diovan , the number one selling branded high blood pressure medicine worldwide, and aliskiren, the active ingredient in Tekturna, the only approved direct renin inhibitor (DRI). The combination offers significantly greater blood pressure reduction than either valsartan or aliskiren alone.

"When it comes to diagnosing and treating high blood pressure, there is a real need for innovative therapies that help patients get to a healthier blood pressure range," said John Flack, M.D., Valturna investigator, and Chairman of the Department of Internal Medicine, Wayne State University, Detroit. "Now for the first time, we have a treatment option in one pill that targets two key points of the RAAS, which may be overactive in many hypertensive patients."

This approval was primarily based on a pivotal eight-week randomized, double-blind, placebo-controlled clinical trial in approximately 1,800 patients, which studied aliskiren 150 mg and 300 mg and valsartan 160 mg and 320 mg alone and in combination. The initial doses of aliskiren and valsartan were 150 mg and 160 mg, respectively, and were increased at four weeks to 300 mg and 320 mg, respectively.

Blood pressure reductions with the aliskiren/valsartan combination were significantly greater than with the monotherapies or placebo at the eight-week primary endpoint. Mean systolic and diastolic blood pressure reductions from baseline were 17.2/12.2 mmHg for aliskiren 300 mg/valsartan 320 mg, compared with 12.8/9.7 mmHg for valsartan 320 mg, 13.0/9.0 mmHg for aliskiren 300 mg, and 4.6/4.1 mmHg for placebo (p<0.05>.

For more information, read these PubMed abstracts:

Yamamoto E, Kataoka K, Dong YF, Nakamura T, Fukuda M, et al. Aliskiren enhances the protective effects of valsartan against cardiovascular and renal injury in endothelial nitric oxide synthase-deficient mice. Hypertension. 2009 Sep;54(3):633-8. Epub 2009 Jul 13.

• Geiger H, Barranco E, Gorostidi M, Taylor A, et al. Combination therapy with various combinations of aliskiren, valsartan, and hydrochlorothiazide in hypertensive patients not adequately responsive to hydrochlorothiazide alone. J Clin Hypertens (Greenwich). 2009 Jun;11(6):324-32.
• Yarows SA, Oparil S, Patel S, Fang H, Zhang J. Aliskiren and valsartan in stage 2 hypertension: subgroup analysis of a randomized, double-blind study.
  Adv Ther. 2008 Dec;25(12):1288-302.
• Tato AM, García López F. [Is the combination aliskiren /valsartan as effective and safe as either drug in monotherapy for treating hypertension?] Nefrologia. 2008;28 Suppl 2:10-1. (Spanish).
• Oparil S, Yarows SA, Patel S, Fang H, Zhang J, Satlin A. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet. 2007 Jul 21;370(9583):221-9
• Chrysant SG, Murray AV, Hoppe UC, Dattani D, Patel S, Hsu H, Zhang J. Long-term safety, tolerability and efficacy of aliskiren in combination with valsartan in patients with hypertension: a 6-month interim analysis. Curr Med Res Opin. 2008 Apr;24(4):1039-47. Epub 2008 Feb 27.