Orphan Drug Sorafenib Tosylate (Nexavar) for Hepatocellular Carcinoma in EU

April 24, 2006

On April 18, the European Commission approved orphan drug status for

sorafenib tosylate (Nexavar tablets, made by Onyx Pharmaceuticals, Inc, and

Bayer Pharmaceuticals Corporation; marketed by Bayer) in the treatment of

hepatocellular carcinoma (HCC).

Sorafenib is an oral 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 in part on data from a phase 2, single-agent study

showing that 43% of patients receiving sorafenib experienced stable disease

for at least 4 months; an additional 9% of patients experienced tumor

shrinkage.

The drug's toxicity profile was similar to that associated with use of

sorafenib in patients with renal cell carcinoma. Fatigue (9.5%), diarrhea

(8%), and hand-foot skin reaction (5%) were most commonly reported.

In a study for a previous approval, sorafenib was linked to an increased

incidence of cardiac ischemia/infarction (2.9% vs 0.4%) and bleeding (15% vs

8%) compared with placebo. Because of the risk for hypertension early in the

course of therapy, weekly monitoring of blood pressure is recommended during

the first 6 weeks of treatment.

According to a company news release, approximately 626,000 cases of HCC were

reported worldwide (15,000 in the United States and 53,600 in Europe), and

more than 600,000 deaths (about 13,000 Americans and 57,000 Europeans) due

to HCC were reported. The 5-year relative survival rate is about 7%.

Sorafenib was previously approved by the US Food and Drug Administration and

Switzerland's regulatory authority Swissmedic in December 2005 and March

2006, respectively, for the treatment of adults with advanced renal cell

carcinoma after nephrectomy and prior palliative or adjuvant therapy with

cytokines (such as interleukin 2 and interferon).

According to the news release, other potential indications for sorafenib

include advanced hepatocellular carcinoma, metastatic melanoma, and

non-small cell lung cancer.

Reviewed by D. Vogin, MD

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