EU Agency to Review Other PAH Drugs

December 21, 2010

December 21, 2010 (London, United Kingdom)— The European Medicines Agency is to review the hepatotoxic profile of two other endothelin receptor antagonists (ERAs) for the treatment of pulmonary arterial hypertension (PAH) following the withdrawal last week of Pfizer's ERA sitaxentan (Thelin) due to two cases of fatal liver injury linked to the drug [1].

The EMA's Committee for Medicinal Products for Human Use (CHMP) today said it would look at bosentan (Tracleer, Actelion) and ambrisentan (Volibris, GlaxoSmithKline), because liver toxicity "may be a class effect." It will begin a cumulative review of the hepatotoxic profile of these ERAs to confirm that they remain a valuable option in the treatment of pulmonary hypertension.

The CHMP has also reviewed three deaths possibly associated with sitaxentan--one occurred in the UK in 2009 and two during clinical trials in India and Ukraine in 2010. It concludes that two of the cases of fatal liver injury were causally related to sitaxentan, and it says the "new data suggest that serious hepatic toxicity cannot be prevented in all patients." In addition, "the cases were not associated with identifiable risk factors, could not be detected by frequent monitoring, and did not resolve with the discontinuation of sitaxentan."

It notes that other medicines indicated in the EU for pulmonary hypertension include tadalafil (Adcirca, United Therapeutics), sildenafil (Revatio, Pfizer), and iloprost (Ventavis, Bayer).

processing....