FDA Approves One Endothelin Antagonist for PAH, Nixes Another

June 26, 2007

June 26, 2007 (Rockville, MD) - The US Food and Drug Administration (FDA) has given the thumbs-up to one endothelin receptor antagonist for the treatment of pulmonary arterial hypertension (PAH) and a provisional thumbs-down to another.

Ambrisentan (Letairis, Gilead Sciences) was approved on the strength of two phase 3 trials that suggested it significantly improves six-minute-walk test results and delays worsening of PAH, the agency announced on June 15, 2007 [1].

On the same day, Encysive Pharmaceuticals, the maker of another drug in the same class, sitaxsentan (Thelin) announced that the FDA has for the third time rejected its application to market the drug for the same indication [2]. But the FDA signaled its willingness to consider the results of an additional study designed to show whether the drug could improve exercise capacity, according to the company.

Ambrisentan is classified as an orphan drug, which has qualified Gilead Sciences for tax credits and marketing incentives, the FDA notes. The drug joins several other available treatments for PAH, including bosentan (Tracleer, Actelion Pharmaceuticals), another endothelin antagonist, and sildenafil (Revatio, Pfizer), the phosphodiesterase inhibitor famously available, in different packaging, for the treatment of erectile dysfunction (Viagra, Pfizer).

In its own statement, Gilead Sciences notes that ambrisentan's approval is for patients with PAH who are in World Health Organization (WHO) symptom class 2 or 3 [3]. Bosentan is indicated for patients with somewhat more severe disease, WHO class 3 or 4. The company claims that its drug may be preferable to bosentan for patients who have experienced transient, asymptomatic liver enzyme elevations on bosentan, citing supporting evidence from an uncontrolled, 36-patient open-label study.

In its story today on the ambrisentan approval [4], the New York Times notes that the "once-a-day pill will cost $3940 a month, about the same as Tracleer." Gilead Sciences, notes Times medical reporter Andrew Pollack, said it is "establishing programs to help uninsured or underinsured patients obtain the drug."

  1. Food and Drug Administration. FDA approves new orphan drug for treatment of pulmonary arterial hypertension [press release]. June 15, 2007. Available at: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01653.html.

  2. Encysive Pharmaceuticals. FDA issues third approvable letter for Thelin (sitaxsentan sodium) [press release]. June 15, 2007. Available at: http://www.encysive.com/news_20070615.html.

  3. Gilead Sciences. US Food and Drug Administration approves Gilead's Letairis, (ambrisentan) 5 mg and 10 mg tablets for the once-daily treatment of pulmonary arterial hypertension (WHO Group 1) in patients with WHO functional class II or III symptoms [press release]. June 15, 2007. Available at: http://www.gilead.com/wt/sec/pr_1016053.

  4. Pollack A. Gilead's drug is approved to treat a rare disease. New York Times, June 16, 2007. Available at: http://www.nytimes.com/2007/06/16/business/16gilead.html?_r=1&ref=health&oref=slogin.

The complete contents of Heart wire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.


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