By Kim Coghill

Washington Editor

Actelion Ltd. expects to launch Tracleer (bosentan), an oral treatment for pulmonary arterial hypertension, by the end of the year.

Actelion said it received an approvable letter for Tracleer from the FDA. ¿We will now work with the FDA to finalize the label,¿ Roland Haefeli, Actelion¿s vice president for corporate communications, told BioWorld Today.

Actelion, based in Allschwil, Switzerland, with offices in South San Francisco, signed a potential $140 million U.S. co-promotion deal with Genentech Inc., also of South San Francisco, for the product last year. The deal, which included a $35 million up-front payment, stipulated that Actelion would take the lead in development and commercialization. (See BioWorld Today, Dec. 14, 2000.)

Aside from working on the label, the FDA¿s letter said approval is contingent upon the implementation of appropriate patient-monitoring measuring regarding liver enzymes and pregnancy prevention. Such measures had already been discussed on Aug. 10 when the FDA¿s Cardiovascular and Renal Drugs Advisory Committee unanimously recommended approval of the product.

Patients suffering from pulmonary arterial hypertension (PAH), a lung disease, cannot pump blood through their lungs sufficiently enough to get oxygen needed for daily activities or exercise. Treatment options are a lung transplant or an intravenous therapy known as Flolan (epoprostenol). Flolan, developed by GlaxoSmithKline plc, is made from a naturally occurring molecule in the body called prostaglandin. Studies have shown that Flolan, which costs about $100,000 annually per patient, can extend life expectancy by three to five years.

Haefeli said the cost of Tracleer, a twice-daily pill, has not been determined, but analysts estimate it will cost about $30,000 per year per patient, possibly generating upwards of $25 million next year for Actelion.

Tracleer, an orphan drug, could help the 100,000 people in the U.S. and Europe who suffer from PAH. Data from Phase III trials of Tracleer in chronic heart failure patients are expected to be released in the first quarter next year.

Haefeli also said Tracleer is being studied in patients who are using Flolan. So far, Actelion has not tested Tracleer with Remodulin (formerly Uniprost, or UT-15), a subcutaneous treatment for PAH developed by United Therapeutics Corp. (UTC), of Silver Spring, Md.

Remodulin received recommended approval in August by the Cardiovascular and Drugs Advisory Committee for the same indication. (See BioWorld Today, Aug. 12, 2001.)

Back in August, Martine Rothblatt, UTC¿s CEO, told BioWorld Today that he would like to see patients use Tracleer and UT-15 together.

None of these products dramatically changes the mortality rate of PAH patients; rather, the drugs help patients feel more comfortable.

In its FDA hearing, Actelion presented data from two successful Phase III pivotal studies that showed improved exercise capacity of patients.

The first trial was a double-blind, placebo-controlled study involving 32 patients at six centers (five in the U.S. and one in France). At 12 weeks, patients in the Tracleer group demonstrated a 20 percent increase in exercise ability compared to placebo in the standardized six-minute walk test (p=0.018). Tracleer patients improved their timed walk distance by a mean of 72 meters, and there was a 40 percent net difference in cardiac output in favor of Tracleer compared to placebo.

The supplemental trial, called BREATHE-1 (Bosentan: Randomized Trial of Endothelin Receptor Antagonist Therapy for Pulmonary Hypertension), was a double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of two twice-daily dose levels of Tracleer.

Patients receiving the medicine were able to walk statistically significantly greater distances in the six-minute walk test after 16 weeks, compared to placebo. The product also was well tolerated, according to the company.

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