Washington Editor

The FDA approved a new drug for high blood pressure, Tekturna (aliskiren), a first-in-class product partnered between Speedel Group and Novartis AG.

"There hasn't been a new tool for the toolbox in over a decade, in terms of a new mechanism of action," said Frank LaSaracina, a managing director at Basel, Switzerland-based Speedel. He added that "the vast majority" of hypertensive patients who seek treatment don't achieve target blood pressure levels - fewer than 60 percent - according to the American Heart Association, so they're still at increased risk for strokes, heart attacks, kidney failure, heart failure and death.

Given that physicians often prescribe more than one drug to reach that goal, "our sense is that there is a significant demand" for something new, he said. "The need is real."

Tekturna is the first high blood pressure drug that acts by inhibiting renin, a kidney enzyme associated with the regulation of blood pressure. That means the new molecular entity works at the beginning of the blood pressure regulation process - rennin is the key enzyme atop the renin angiotensin system - while other commercial high blood pressure medications act at later stages, downstream in the cascade.

"The point of activation of this entire cascade is really at the point of renin," LaSaracina told BioWorld Today. "Renin is really needed to drive blood pressure up, so by blocking the cascade at its point of activation, the top, you stand a good chance of more efficiently modulating the system downward."

Novartis, also of Basel, expects to launch the once-daily oral tablet later this month. Its price has yet to be disclosed. LaSaracina said the partners believe it has a five-year lead on any direct competitors still in development.

The drug was approved for use as monotherapy and in combination with other anti-hypertensives such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and hydrochlorothiazide, a diuretic. That fairly broad label positions Tekturna for large-market use in a patient population estimated to number nearly 1 billion people worldwide, according to a Novartis press release. LaSaracina said about 190 million people have high blood pressure in seven key markets: the U.S., Germany, France, the UK, Italy, Spain and Japan. The FDA said the lifelong condition, sometimes called the silent killer, affects about one-quarter of all Americans.

Tekturna's effectiveness in lowering blood pressure was demonstrated in six placebo-controlled trials that included more than 2,000 patients with mild to moderate hypertension. It produced double-digit reductions in blood pressure sustained for a full 24 hours, reaching its maximum lowering effect within two weeks. The effect was maintained for up to one year, and further blood pressure reductions were achieved when used in combination with hydrochlorothiazide.

"We believe that renin inhibitors will become a gold standard in the treatment of hypertension," LaSaracina said, also noting that Tekturna's long half-life helps patients avoid bumping their blood pressure when missing a day. "So should a dose or two be missed, it certainly appears that the patient would be protected." Tekturna was evaluated for safety in more than 6,460 patients, including 1,740 treated longer than six months and more than 1,250 for more than a year, and generally was well tolerated at the approved doses of 150 mg and 300 mg.

Novartis filed its new drug application last spring, based largely on that body of data. Speedel is due royalties of an undisclosed amount on sales going forward, providing "a sustainable revenue stream" for the first time in the company's history, LaSaracina said. (See BioWorld Today, April 21, 2006.)

Originally called SPP100, it was in-licensed by Speedel in 1999 and advanced through Phase I and II trials under its watch before Novartis exercised a license-back option in 2002. Speedel is not a participant in its commercialization. The drug remains under regulatory review in Europe, where its proposed brand name is Rasilez, and approval there is expected late this year or early next year.

Speedel, which already has received all milestone payments from Novartis per terms of their relationship, is itself developing next-generation renin inhibitors to follow Tekturna with improved bioavailability and tissue penetration: SPP635 is in Phase IIa, with data due before the end of the third quarter, and SPP1148 is in Phase I, with those data expected before the end of this year. Novartis does not have rights to those products, nor any backups or additional renin programs.

Beyond that research, Speedel's portfolio also includes another product that's reached Phase III, SPP301, an endothelin A receptor antagonist for diabetic nephropathy. However, its development is on hold as its registration was stopped early. The company's pipeline also features a thrombin inhibitor, SPP200, in Phase II for reducing occlusions in hemodialysis patients, and other preclinical projects.

Tuesday, the company's stock (SWX:SPPN) gained CHF8.20 on the Swiss Stock Exchange to close at CHF195.20 (US$159.50).

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