Global pharma companies are now looking at the option of developing novel molecules to control blood pressure that target the renin-angiotensin aldosterone system (RAS). Early this year, Novartis has obtained an approval from the US FDA for its first in class antihypertensive, Tekturna (Aliskiren), a new class of completely non-peptide, low-molecular weight, orally active transition-state renin inhibitor. The molecule acts on RAS, which has a broad pathological role in causing a variety of renal and cardiovascular diseases.

Aliskiren, is the first-ever US FDA approved renin inhibitor. It was synthesized based on the knowledge of the three-dimensional structure of recombinant human renin. The molecule binds with the active site of the enzyme specificity pockets. It induces conformational changes that affect (pro) renin receptor binding, stated Dr. G. Jagadeesh, expert pharmacologist, Division of Cardiovascular and Renal products, US FDA.

The approval for Tekturna was based on solid clinical trial data supporting its effectiveness in controlling blood pressure, he said during a presentation on the occasion of the 40th annual conference of the Indian Pharmacological Society meeting held from Nov 1 to 3, 2007 at NIPER in Chandigarh.

According to Dr. Jagadeesh, there are five major steps at which the RAS can be interrupted. ACE inhibitors block angiotensin I to angiotensin II conversion. The effect of angiotensin II at AT-1 receptor site is antagonized by angiotensin II receptor blockers which inhibits sodium re-absorption and increases volume by aldosterone antagonists. The ACE and neutral endopeptidase activities are simultaneously blocked by vasopeptidase inhibitors.

Dr. Jagadeesh stated that renin inhibitors in hypertension treatment are new therapeutic opportunities before pharma companies. In fact cardiovascular disorders which are becoming a bigger killer than cancer are seeing fewer new drugs compared to the oncology pipeline which is proving to catch the interest of every other pharma giant.

The last drug targeting RAS approved by the US FDA for hypertension was in 2000 and it took over five years for a company like Novartis to come out with a novel and advanced molecule.

So long ACE inhibitors (Ramapril, Captopril) have been the most opted drugs for control of hypertension. But in 1995, Cozaar of Merck was recognized as a new class of hypertension medicines in the angiotensive receptor blocker category. Now with top class renin enzyme inhibitors, pharma companies and cardiovascular disease specialists will have a new drug to control hypertension which affects over one billion people worldwide and still uncontrolled in nearly 70 per cent of patients.. If untreated, it carries a high mortality rate. Risk factors for hypertension include family history, stress, obesity, a diet high in saturated fats or sodium, tobacco use, sedentary lifestyle and aging.

According to pharma analysts, growth of the hypertension market is estimated grow to nearly $30 billion by 2010. In India the market size is Rs. 1,500 crore. Leading players in the hypertension drug arena are Ranbaxy, Dr. Reddys, Lupin, Aurobindo Pharma, Sun Pharma Micro Labs, Bal Pharma to name a few.