International Approvals: Nexavar, Elaprase, Aranesp

Yael Waknine

November 04, 2007

November 5, 2007 -- The European Commission (EC) has approved sorafenib tosylate for the treatment of adult hepatocellular carcinoma; Japan's Ministry of Health, Labor, and Welfare has approved idursulfase 2 mg/mL solution for the treatment of Hunter syndrome; and the EC has lifted the pediatric age restrictions for darbepoetin alfa in chronic renal failure.

Sorafenib Tosylate ( Nexavar) for Hepatocellular Carcinoma in EU

On October 30, the European Commission (EC) approved sorafenib tosylate tablets ( Nexavar, manufactured by Onyx Pharmaceuticals, Inc, and Bayer Pharmaceuticals Corporation; marketed by Bayer) for the treatment of adults with hepatocellular carcinoma (HCC).

"The approval of Nexavar, a novel multi-kinase inhibitor, represents an unprecedented advance for patients with HCC who, until now, had no approved systemic treatment options," says Arthur Higgins, chairman of the Executive Committee of Bayer HealthCare, in a company news release.

Sorafenib is a multikinase inhibitor that targets serine/threonine and receptor tyrosine kinases to decrease tumor growth and angiogenesis. Preclinical models demonstrated the drug's activity against RAF kinase, VEGFR-2, VEGFR-3, PDGFR-B, KIT, and FLT-3.

The approval was based on data from a multicenter, double-blind, phase 3 randomized Sorafenib HCC Assessment Randomized Protocol (SHARP) trial, showing that treatment with sorafenib significantly increased overall survival by 44% relative to placebo (10.7 vs 7.9 months; hazard ratio, 0.69; P = .0006)

According to the news release, no indication of imbalances was observed between groups in terms of serious adverse events; the most commonly observed sorafenib-related effects were diarrhea and hand-foot syndrome.

This indication for sorafenib is currently under review by the US Food and Drug Administration (FDA) and Japan's Ministry of Health, Labor, and Welfare. Sorafenib previously was approved by the EC and FDA for the treatment of advanced renal carcinoma.

Idursulfase Solution ( Elaprase) for Hunter Syndrome in Japan

On October 4, Japan's Ministry of Health, Labor, and Welfare approved idursulfase 2 mg/mL solution ( Elaprase, manufactured by Shire Human Genetic Therapies, Inc; marketed by Genzyme Corp) for the treatment of Hunter syndrome.

Hunter syndrome is a rare genetic condition caused by an absence or deficiency of iduronate-2-sulfatase, a lysosomal enzyme. It usually becomes apparent in children aged 18 to 36 months and is characterized by symptoms such as growth delay, joint stiffness, and coarsening of facial features. Severe cases can lead to respiratory and cardiac problems, liver and spleen enlargement, neurologic deficits, and death.

Idursulfase is a purified form of iduronate-2-sulfatase and is produced by recombinant DNA technology in a human cell line. The recommended dose is 0.5 mg/kg of body weight administered every week as an intravenous infusion for a period of 1 to 3 hours.

Previously, idursulfase was approved by the US Food and Drug Administration, Health Canada, and the European Commission.

Pediatric Age Restriction for Darbepoetin Alfa (Aranesp) Lifted in EU

On September 28, the European Commission (EC) approved an expanded indication for darbepoetin alfa ( Aranesp, Amgen GmbH), allowing its use in all pediatric patients with anemia related to chronic renal failure. Previously, its use had been restricted to patients aged 11 years and older.

Prescribing guidelines will be given separately for adult and pediatric patients, the company says in a news release, noting that darbepoetin has not been studied in children aged less than 1 year.

Darbepoetin alfa is approved by the EC and US Food and Drug Administration for the treatment of anemia associated with chronic renal failure and chemotherapy-induced anemia in patients with nonmyeloid malignancies.

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