Washington Editor

A drug developed in part by the Speedel Group, SPP100 (aliskiren), now is under FDA review after Novartis AG filed for regulatory approval of the hypertension treatment.

The Swiss firms have proposed the trade name Rasilez. Speedel, of Basel, already received all milestone payments from Novartis per terms of their relationship. The new drug application seeks to market the renin inhibitor as monotherapy and in combination with other anti-hypertensives for high blood pressure.

"There hasn't been a new mechanism of action in hypertension for about 10 years," said Frank LaSaracina, the managing director of Speedel's U.S. operations, adding that about 70 percent of hypertensive patients are not adequately controlled by their current therapy. Filing for the approval, he added, "is an important development for these patients and their physicians."

A first-in-class oral product, Speedel spearheaded its Phase I and II development after licensing rights in 1999. Three years later, Novartis exercised a license-back option and eventually began late-stage development. Phase III trials are ongoing in the U.S., Europe and Japan, and Novartis, also of Basel, expects to file for European approval later this year.

Speedel is due undisclosed royalties on Rasilez's eventual sales.

The FDA submission includes data from more than 6,000 high blood pressure patients treated with SPP100 in 34 studies. The findings showed that when used alone, Rasilez produced significant blood pressure reductions, sustained over 24 hours. One of Speedel's Phase II trials, which included 200 patients, demonstrated that SPP100 achieved dose-dependent blood pressure reduction.

Speedel, which last month raised about $64 million in a European offering, said SPP100 has a five-year lead over next-generation renin inhibitors in development. Renin is the key enzyme atop the renin angiotensin system (RAS), which regulates blood pressure. Renin is suppressed by Rasilez, because at that point of activation, "only the renin inhibitor is going to act at the very top," LaSaracina told BioWorld Today. Other products that act on the same cascade work downstream, namely angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor antagonists (ARBs).

"This is a poly-pharmacy marketplace," LaSaracina said of an anti-hypertension environment characterized as large but underserved. "There is not only room [for new products], but there is need."

In addition to acting earlier in the RAS system, renin inhibitors work to reduce Plasma Renin Activity (PRA), a surrogate marker that LaSaracina said is "emerging as an important factor in cardiovascular morbidity and mortality." In contrast, Speedel said most current leading anti-hypertensive drug classes, such as ACE-Is and ARBs, increase PRA levels, although beta-blockers do not.

The company's own renin inhibitors include SPP635, which is in Phase I with results due in the second half of the year, followed by the SPP1100 series, which is in toxicology testing and is expected to lead a compound into human studies before the end of this year. There also is the SPP800 series in late-stage preclinical profiling. Novartis has no additional rights to those products.

Also in the company's portfolio is SPP301, an endothelin-A receptor antagonist in Phase III for diabetic nephropathy. The registration program, which is projected to last three and a half years, began last summer to enroll 2,000 patients in order to measure the drug's ability to reduce morbidity and mortality. Speedel, which is open to partnering possibilities, owns worldwide development and commercialization rights to SPP301. In addition, its pipeline features the thrombin inhibitor SPP200 in Phase II and other preclinical projects.

Shares in Speedel, which last year gained a listing on the Swiss Exchange (SWX:SPPN), were valued at CHF177 (US$138.53) after Thursday's close of business.