Breathless

By Matthew Herper

Victims of a rare and deadly lung disease are getting hope from a slew of new biotech drugs.

At 37 years old, Susan Dodson, an on-the-go banker and mother of two, became so out of breath while running up the stairs of her new house that she almost threw up. Her internist, a close friend, took a chest X ray and found her lungs and heart to be badly damaged. She bounced from specialist to specialist, once even borrowing a client’s private jet, to figure out what was wrong. The ultimate diagnosis: a rare condition called pulmonary arterial hypertension. Dodson had less than two years to live.

That was six years ago. Dodson has not only survived but also managed to carry on a normal life as a vice president at Whitney National Bank in Destin, Fla., thanks to a handful of small biotech companies that decided to develop drugs for her disease even as big pharmaceutical firms dragged their feet. Dodson says the treatments, despite sometimes grueling side effects, have been a miracle for her, though she still has trouble with stairs and strenuous exercise. “It’s like going from close to death, facing mortality and coming back to life,” she says.

Pulmonary arterial hypertension, or PAH, afflicts a mere 200,000 people worldwide, such a rarity that most doctors never even encounter it. The disease begins insidiously, with a gradual increase in blood flow through the artery between the heart and the lungs. As the heart pumps harder, the ensuing pressure damages the artery, causing pressure to increase even more, in a vicious escalation that eventually destroys the heart and lungs.

In Dodson’s case the problem was a hole in the heart wall, but diet pills and genetic factors can also be a trigger. Until ten years ago the only recourse for PAH was a heart or lung transplant, or both, an option not available to the sickest patients.

But in the past five years a handful of approved and experimental drugs have revolutionized the treatment of PAH. Cardiologist Robert Bourge of the University of Alabama at Birmingham has seen his patients go from almost always requiring transplants, with many dying within five to ten years, to almost always being kept healthy with drugs alone. “It’s a remarkable change,” he says. “It’s night and day.”

Many of these drugs, starting with GlaxoSmithkline’s Flolan, introduced in 1995, are variants of prostacyclin, a naturally occurring fat molecule that relaxes the blood vessels to reduce pressure. Pfizer’s Viagra works in a similar way and was initially designed as a PAH drug, but what was first considered a side effect became its main use. Viagra was finally approved for PAH in 2005.

The most impressive advances have come from tiny firms. In November 2001 Actelion in Switzerland introduced Tracleer, a pill that is now the standard of care for many patients and brought in $350 million in the first nine months of 2005. In May 2002 United Therapeutics launched Remodulin, an improved form of Flolan.

Remodulin saved Dodson’s life, but injections of it caused her “excruciating” pain until she switched to a new, inhaled drug called Ventavis, from CoTherix of South San Francisco. She carries Ventavis in her purse and takes it every two hours or so. Pacific Growth Equities forecasts Ventavis sales could triple to $66 million this year. CoTherix’s stock price has nearly doubled since its October 2004 initial offering.

Also on the horizon are two pills that could potentially displace Tracleer: Thelin, from Encysive Pharmaceuticals, which is awaiting federal approval, and ambrisentan, from Myogen. Myogen’s impressive trial results have helped that company’s market capitalization more than triple to $1.25 billion on evidence that the drug could be as effective as and safer than others. “This is a serious disease, and there’s no magic bullet,” says trial leader Lewis Rubin, a pulmonologist at UC, San Diego. “But this has a lot of check marks on the positive side.”