Pfizer voluntarily withdraws sitaxsentan from the market worldwide and halts ongoing clinical trials

Key Points

Based on "a review of emerging safety information from clinical trials and postmarketing reports," Pfizer announced it would be voluntarily withdrawing sitaxsentan (Thelin), the manufacturer's pulmonary artery hypertension (PAH) treatment from the market worldwide. Specifically, 2 cases of idiosyncratic, fatal hepatic failure have been linked to sitaxsentan use.

Sitaxsentan, an endothelin receptor antagonist, has been marketed in 16 countries in Europe since 2006 and Australia and Canada; however, the drug never gained US FDA approval. According to the company's press release, all ongoing clinical trials are being permanently discontinued. This effectively ends any of Pfizer's plans to file a new drug application (NDA) for approval in the United States.

"These findings related to liver toxicity with sitaxsentan were likely not surprising to many," suggested Craig I. Coleman, PharmD, an associate professor of pharmacy practice at the University of Connecticut School of Pharmacy, Storrs. He continued, "Both currently FDA-approved endothelin receptor antagonists include black-boxed warnings in their prescribing information warning of potential risks of liver injury."

A number of alternative treatments are available in the United States for the treatment of PAH including prostacyclin analogues [epoprostenol (Flolan), Iloprost (Ventavis) and treprostinil (Remodulin)], endothelin receptor antagonists [bosentan (Tracleer) and ambrisentan (Letairis)], and phosphodiesterase type-5 inhibitors [tadalafil (Adcirca) and sildenafil (Revatio)]. Of note, sildenafil is also manufactured by Pfizer.

"Given the availability of alternative treatments, Pfizer has concluded that the overall benefit of Thelin no longer outweighs the risks in the general population of PAH patients," the company emphasized in its release.

Pfizer is currently recommending that no new patients be prescribed sitaxsentan and that patients receiving sitaxsentan be transitioned to appropriate alternate therapies as soon as possible. However, they strongly caution patients not to stop taking sitaxsentan until they speak to their healthcare provider.

PAH is a rare, incurable, and life-threatening disease that typically worsens over time. The American Lung Association estimates that the disease affects somewhere between 1 in 100,000 to 1 in 1 million people. Overall, about 50% of patients with PAH die within 5 years of diagnosis.

SOURCES

Pfizer. Pfizer Stops Clinical Trials of Thelin and Initiates Voluntary Product Withdrawal in the Interest of Patient Safety. December 10, 2010. Available at: http://pfizer.mediaroom.com/index.php?s=5149&item=22387. Accessed December 13, 2010.

Tracleer [package insert]. San Francisco, CA: Actelion Pharmaceuticals US, Inc; 2009.

Leteris [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2010.

American Lung Association. Understanding PAH. Available at: http://www.lungusa.org/lung-disease/pulmonary-arterial-hypertension/understanding-pah.html. Accessed December 13, 2010.