New PAH drug improves exercise capacity

July 23, 2007

Ambrisentan (Letairis) from Gilead Sciences, Inc. has been approved by the FDA for patients with PAH (WHO Group 1) with WHO Functional Class II or III symptoms.

Ambrisentan is an en-dothelin receptor antago- nist selective for the endothelin type-A (ET-A) receptor. In PAH, activation of the ET-A receptor by endothelin leads to vasoconstriction and cell proliferation according to the product's prescribing information. Patients with PAH have elevated blood levels of endothelin, up to a 10-fold increase above normal.

Efficacy of ambrisentan was proven in two 12-week phase III clinical trials (ARIES-1 and ARIES-2) involving 393 patients. In both studies, ambrisentan-treated patients experienced a significant improvement in the six-minute walk distance for each dose level (2.5-, 5-, and 10-mg). In addition, improvements increased as the dose increased. Treatment with ambrisentan also significantly delayed time to clinical worsening of PAH.

Ambrisentan was shown to be teratogenic in rats and may cause fetal harm if administered to a pregnant woman. Therefore, pregnancy must be excluded, prior to initiation of treatment, with a negative pregnancy test, and two reliable methods of birth control should be utilized for prevention of pregnancy during ambrisentan administration. Monthly pregnancy tests should be obtained throughout treatment.

According to the prescribing information, the initial dose of ambrisentan is 5 mg once daily, with or without food, and a dosage increase to 10 mg can be considered if 5 mg is well tolerated. Tablets are available in both 5 and 10 mg.

Kevin Young, Gilead's executive VP of commercial operations, said Gilead has set pricing of ambrisentan at $3,940 for a month's supply (30-tablet pack). "Both the 5- and 10-mg tablets are priced the same, ensuring that price is not an impediment if a physician believes the higher dose is the right clinical choice for a patient," he said. Young added that the company has contracted with eight specialty pharmacies that will order the product for specific patients and distribute treatments through the Letairis Education and Access Program (LEAP). Young said the distribution network should reduce the number of situations in which the patient has coverage but is out-of-network.

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