New drug battles 'silent killer'

By Mike Nagle

- Last updated on GMT

Related tags Blood pressure

The first new type of high blood pressure medicine in more than a
decade has been approved in the US, with experts predicting
blockbuster success.

Novartis developed Tekturna (aliskiren) in conjunction with Speedel.

Like other current therapies, the drug is designed to cause blood vessels to dilate and to reduce high blood pressure or hypertension.

However, what sets it apart is that it works in a different way - it is the first drug approved by the US Food and Drug Administration (FDA) that directly inhibits a protein called renin, which can lead to increased blood pressure.

Dubbed the 'silent killer', high-blood pressure is a leading cause of cardiovascular disease, the world's number one killer.

Novartis estimate that nearly 1bn people worldwide suffer from the condition and the hypertension market as a whole is estimated to be worth over $25bn (€19bn), according to a report by Visiongain.

"A direct renin inhibitor such as Tekturna offers an exciting novel therapeutic option for treating hypertension," said Dr Marc Pfeffer, Professor of Medicine at Harvard Medical School.

Although the drug will face stiff competition from other high blood pressure medications on the market, Novartis claim that the condition is uncontrolled in nearly 70 per cent of patients and so there is still a need for new therapies.

"Hypertension is rightly called 'the silent killer' because it usually has no symptoms until it causes major damage to the body organs," said Dr Douglas Throckmorton, deputy director of the FDA's Center for Drug Evaluation and Research.

"Today's approval adds a new safe and effective treatment option for people who need help to control their blood pressure."

There is a cascade of proteins in the body that contributes to increased blood pressure, beginning with renin, which is secreted by the kidneys in response to a drop in blood flow volume and low blood pressure.

Renin then goes on to cleave a protein to form the inactive product, angiotensin I.

This is then converted to angiotensin II by angiotension converting enzyme (ACE).

It is the product of this last reaction that causes blood vessels to constrict and the release of molecules - such as adrenaline and dopamine - that increase blood pressure.

Consequently, there are several areas in the cascade for drug developers to target.

Unlike other currently marketed drugs, which work 'downstream' in the pathway, Tekturna inhibts renin directly, exerting its effect during the very first step.

A report released on Monday from Decision Resources called 'Hypertension' predicts that Tekturna will achieve blockbuster status and take up to a $2.1bn slice of the market by 2015.

However, this is only if further clinical trials demonstrates that the drug can prevent organ damage superior to a different angiotensin II receptor blockers.

Industry analysts, although not looking that far ahead, are also predicting the new drug will be a success.

Les Funtleyder at Miller Tabak suggests the drug could make $1bn slice by 2011, with a similar estimate from Joe Tooley at AG Edwards.

So far, Tekturna has been shown to be safe to use for up to a year and Novartis stated that it would also conduct further clinical trials to test the long-term effects of using the drug.

Established hypertension drug classes affect other areas of the pathway.

ACE inhibitors, reduce the amount of angiotensin II produced.

Many drugs in this class are already off patent and Abott's Mavik (trandolapril) is due off patent later this year with Solvay Pharmaceuticals' Aceon/Coversyl (perindopril) due to lose patent protection in 2009.

A second class of drugs is the angiotensin II receptor blockers (ARBs).

Designed to prevent angiotensin II from being able to increase blood pressure, drugs in this class include Merck & Co's Cozaar (losartan) and Novartis' Diovan (valsartan).

Avapro (irbesartan) is jointly marketed by Bristol-Myers Squibb and Sanofi-aventis and had combined sales last year of $3.4bn.

Other classes of drugs used to treat hypertension are calcium channel blockers, endothelin receptor blockers, diuretics and beta-blockers.

Patients with high blood pressure often receive more than one drug, across different drug classes and in different combinations.

One example of a combination therapy that reaches across drug classes is Novartis' Exforge, which is a combination of the ARB Diovan (valsartan) and Norvasc (amlodipine), a calcium channel blocker from Pfizer.

The drug was tentatively approved last December but isn't expected to be available to patients until September 2007, pending patent expiry for Norvasc.

Daiichi Sankyo is also taking advantage of Norvasc losing patent protection by combining it with its own hypertension product, Benicar (olmesartan).

The Decision Resources report predicts that both combination therapies will also both reach blockbuster status with sales of $3.2 billion and $1.9 billion respectively.

"Fixed-dose combinations such as Exforge and amlodipine/olmesartan have the potential to reduce side effects and help to lessen the increasing number of pills patients need to take - two crucial issues in patient compliance with treatment," said Decision Resources analyst Jeremy Goldman.

"As a result, the use of combination therapy to treat hypertension will double from 20% to 40% of patients between 2005 and 2015," he added.

The emergence of Tekturna will add another drug to the complicated array of options for clinicians.

"Many patients require two or more medicines to control their blood pressure.

As a new treatment approach, Tekturna has the potential to help these patients manage their disease," said James Shannon, global head of development at Novartis Pharma.

"Tekturna demonstrates our commitment to developing innovative medicines to help the millions of patients suffering from high blood pressure," he concluded.

Related topics Preclinical Research

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