New Option For Rare Condition

People with a rare and lethal high blood pressure now have more options for convenient treatment with less drug toxicity.

Late Friday the Food and Drug Administration approved Letairis, a pill made by Gilead Sciences Inc. for the treatment of pulmonary arterial hypertension, in which lung vessels constrict, raising blood pressure and leading to heart failure.

Mysterious and often misdiagnosed, PAH can arise without warning. It also can result from diseases like scleroderma or advanced HIV, or the diet drug combo known as fen-phen. Based on market research, Gilead, of Foster City, Calif., estimates 75,000 to 90,000 people in the U.S. have PAH, over half of them undiagnosed.

About a half-dozen PAH drugs exist, all of them expensive, including round-the-clock infusions and some oral drugs that risk birth defects and liver damage. Some patients require lung transplants, though drug therapy can stave off the need for it. Letairis's label carries a black-box warning about such risks, but the company and some analysts say it has the best safety profile of any oral drug to date. Shashi Sahgal, a 42-year-old homemaker and mother of two teenagers in Mission Viejo, Calif., was hiking and bounding up stairs two at a time back in 2002. When she felt winded, doctors thought she had exercise-induced asthma. By the end of 2002, exhaustion and an enlarged heart led doctors to perform a right-heart catheterization. That nailed the diagnosis of PAH.

Without treatment, PAH can be fatal within three years. Referred to lung specialist Ronald Oudiz of Harbor UCLA Medical Center in Torrance, Calif., Mrs. Sahgal entered a trial of the new Gilead drug, then known by its generic name ambrisentan. "It made a huge difference," she says.

Gilead acquired ambrisentan as part of its merger with Myogen Inc. last November, and it now plans to launch sales in the U.S. this week. Under a co-marketing agreement with GlaxoSmithKline PLC, GSK is seeking approval to market the drug outside the U.S. On Friday, the FDA delayed action on another PAH drug, Thelin by Encysive Pharmaceuticals Inc. of Houston, urging more studies.

The first drug approved for the condition in 1995 was GSK's Flolan, an infusion given continuously through a chest catheter. Originally designed as a bridge to a transplant, the drug treatment alone has extended some of his patients' lives by 13 or 14 years, says UCLA's Dr. Oudiz. Gilead now sells Flolan in the U.S., while GSK markets it outside the US.

United Therapeutics Corp., Silver Spring, Md., markets a similar drug, Remodulin, which is given as a subcutaneous or intravenous infusion. A pill form is being studied.

Swiss drug maker Actelion Ltd. markets an inhaled drug, Ventavis. It also markets a pill, Tracleer, part of an oral-drug family that expands vessels but can cause liver damage or birth defects.

Gilead's Letairis is also part of the same drug family, known as ERAs (endothelin receptor antagonists, which work by relaxing blood vessels). Gilead says its studies show Letairis has a lower incidence of liver toxicity than rival products. Common side effects include peripheral edema (or swelling), nasal congestion, flushing and palpitations. Patients must have liver enzymes monitored to detect any signs of damage, and women -- who account for most PAH patients -- must avoid becoming pregnant.

Pfizer Inc. entered the field after discovering its erectile-dysfunction drug, Viagra, could benefit vessels of the lungs as well. The New York company rechristened the drug as Revatio for PAH. Another such drug, Indianapolis-based Eli Lilly & Co.'s Cialis, is now in tests for PAH.

Like other orphan drugs for rare but serious diseases, PAH treatment is costly. A year of Flolan can run $100,000, while Tracleer tops $40,000, according to Gilead officials.

On Friday, Gilead said it set the price of Letairis at $3,940 a month, or $47,280 a year, using Tracleer's pricetag as a benchmark. The company plans to offer patient assistance with reimbursement, as well as some discounts and free drugs to patients lacking coverage.

A year of Revatio given as a thrice-daily 20-milligram tablet is about $10,000, says Dr. Oudiz. But for uninsured patients who are taking higher doses, he says it is less costly to take the drug as Viagra.

Dr. Oudiz has received funding support from Actelion, Gilead, Pfizer, United Therapeutics, Encysive and Lilly.

Like many patients who move to combination therapy, Mrs. Sahgal now also takes Revatio, along with the blood-thinner coumadin to prevent clots.

"I still can't go uphill fast, and I'm not going to climb Mt. Everest," says Mrs. Sahgal, now 46. But she adds, "If all goes well, we're looking at 20-plus years."