By Kim Coghill
BETHESDA, Md. ¿ In one week¿s time, the estimated 100,000 patients who suffer from pulmonary arterial hypertension (PAH) have been given two potential treatment options.
In a unanimous 9-0 vote Friday, the Cardiovascular and Renal Drugs Advisory Committee of the FDA recommended approval of Tracleer (bosentan), a twice-daily pill for PAH developed by Actelion Ltd., of Switzerland and South San Francisco, and its partner, Genentech Inc., also of South San Francisco.
The FDA makes the final decision on drug approval and typically follows the committee¿s advice.
Simon Buckingham, Actelion¿s U.S. president, told BioWorld Today that the company hopes for a fourth-quarter launch. Actelion will lead the commercialization effort for Tracleer. The product also is in Phase III trials for chronic heart failure.
JoAnn Lindenfeld, committee reviewer and professor of medicine at the division of cardiology at the University of Colorado Health Science Center in Denver, called Tracleer ¿clearly effective,¿ with only a few safety problems such as some liver toxicity, hematologic toxicity and teratogenic effects.
¿The safety data is not ideal, but I believe the risk is down to a comfortable level,¿ Lindenfeld said. ¿But I don¿t think there¿s a serious problem here.¿
Steve Nissen, a committee member and vice chairman of the department of cardiology and professor of medicine at Ohio State University, the Cleveland Clinic Foundation, called Tracleer a ¿major therapeutic breakthrough.¿
In a 6-3 vote by the same committee Thursday, Silver Spring, Md.-based United Therapeutics Corp. (UTC) was granted recommended approval of Remodulin (formerly Uniprost or UT-15), a subcutaneous treatment for PAH. Both Remodulin and Tracleer are orphan drugs.
The only treatment currently available for the indication is Flolan (epoprostenol), a continuous infusion developed by GlaxoSmithKline plc. Flolan is made from a naturally occurring molecule in the body called prostaglandin. Studies have shown that Flolan, which costs about $100,000 a year, can extend life expectancy by three to five years. Tracleer will probably cost about $30,000 annually, and some estimates show the pill could generate $25 million in 2002.
Martine Rothblatt, UTC¿s CEO, attended Actelion¿s hearing Friday and after the vote told BioWorld Today that the committee¿s decision was good for UTC. She hopes patients will use Tracleer and UT-15 together.
In December UTC said it estimates that in its first six months of sales, Remodulin is expected to generate about $8 million to $10 million. Rothblatt said Friday the company has not worked up a price for the drug.
None of the three products dramatically changes the mortality rate of PAH patients; rather, the drugs help patients feel more comfortable.
PAH is a rare lung disease that Buckingham characterized as ¿essentially high blood pressure in the lungs.¿ Patients cannot pump blood through their lungs sufficiently enough to get the oxygen needed for daily activities or exercise. Aside from intravenous therapy, the only other treatment currently approved is a lung transplant.
Pivotal Studies Met Endpoints
The company presented data Friday 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.
Actelion and Genentech also have filed for approval in the European Union, Canada, Switzerland and Australia.