Kidney cancer drug Pazopanib (Votrient) of GSK could lead to liver damage: US FDA

Pazopanib (Votrient), an experimental kidney cancer drug from GlaxoSmithKline could lead to severe liver injury, according to US FDA.

New findings on Pazopanib (Votrient) by the US FDA panel of experts could delay the approval of the kidney cancer drug in US.

Experts in US FDA noted three deaths related to liver damage with the drug. They also found  elevated levels of enzymes that often predict liver damage.

Besides possible liver damages, pazopanib (Votrient) is also linked to side effects common to other cancer drugs, including hypertension, internal bleeding and blood clots.

Pazopanib family of drug slow progression of liver cancer by blocking enzymes that promote tumor growth.

“The FDA is concerned about the benefit-to-risk ratio of pazopanib in the intended population of patients,” the agency said in the documents.

Pazopanib (Votrient) is an investigational, oral, once-daily angiogenesis inhibitor targeting VEGFR, PDGFR and c-kit. VEGF and PDGF are growth factors critical to the development and growth of blood vessels – a process known as angiogenesis. Angiogenesis plays a pivotal role in the growth and spread of several tumour types, with VEGF and PDGF over-expression linked to multiple cancers.

Once-daily pazopanib (Votrient) reduced the risk of tumor progression or death by an average of five months, or 54 percent, compared with a placebo pill, according to a study Glaxo submitted as part of its new drug application.

GlaxoSmithKline completed the submission of a new drug application (NDA) to the US Food and Drug Administration (FDA) for pazopanib (Votrient) as an oral therapy for patients with advanced renal cell carcinoma in December 2008.

GlaxoSmithKline also submitted a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMEA) for pazopanib as an oral therapy for patients with advanced and/or metastatic renal cell carcinoma, in March.

Glaxo’s MAA submission on pazopanib is based on positive results from a randomised, double-blind, placebo-controlled Phase III study of pazopanib in treatment-naïve and cytokine-pre-treated patients with advanced renal cell carninoma or kidney cancer.

Pazopanib is also being evaluated as a monotherapy,in combination with targeted therapies and in combination with cytotoxic chemotherapy. More than 2,000 patients have been treated to date in clinical trials.

Renal cell carcinoma is the most common type of kidney cancer. The incidence of renal cell carcinoma is rising throughout the world with 208,000 new cases diagnosed annually, and over 100,000 deaths. More than 10 percent of new cases are diagnosed in Western Europe, Glaxo release stated.

In US, an estimated 57,760 new cases of kidney cancer will be diagnosed this year, and almost 13,000 people will die of the disease. Advanced kidney cancer killed about 13,000 people in the U.S. last year, according to the American Cancer Society.

US FDA has approved five new treatments for the disease, including Pfizer’s Sutent and Bayer’s Nexavar, since 2005. Sutent generated revenue of $847 million last year for Pfizer.