Orphan Drug Status Granted to Sorafenib for Liver Cancer

Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals, Inc, announced recently that the oral agent sorafenib (Nexavar) has been granted orphan drug status for the treatment of hepatocellular carcinoma by the US Food and Drug Administration (FDA). A similar designation has been granted by the European Commission.

"We are very encouraged by the collaboration of the FDA as well as the European Regulatory bodies in our research surrounding this highly fatal disease," said Susan Kelley, MD, who is vice president of Oncology at Bayer Pharmaceuticals Corporation. "It fuels our efforts to strive toward a novel therapy for liver cancer patients worldwide."

Clinical Trials

At the 16th American Association for Cancer Research-National Cancer Institute-European Organization for Research and Treatment of Cancer (AACR-NCI-EORTC) meeting in 2004, investigators reported that in a phase II single-agent study, 43% of patients treated with sorafenib experienced stable disease for at least 4 months and an additional 9% of patients experienced tumor shrinkage. The most common grade 3/4 drug-related toxicities were fatigue (9.5%), diarrhea (8%), and hand-foot skin reaction (5%). The toxicity profile of sorafenib was similar to that seen in a previously reported safety analysis conducted in patients with renal cell carcinoma.

A phase III trial of sorafenib administered as a single agent is ongoing. It is designed to measure differences in overall survival, time to symptom progression, and time to tumor progression of sorafenib vs placebo in liver cancer patients. A randomized phase II trial for liver cancer patients to evaluate the efficacy of Nexavar in combination with the chemotherapeutic agent doxorubicin is also ongoing.

"Liver cancer is such an aggressive disease that patients diagnosed with it rarely live beyond 2 years," said Dr. Jordi Bruix, head of the Barcelona Clinic Liver Cancer Group at the University of Barcelona in Spain. "The global medical community recognizes the need for new treatments in liver cancer, and I am hopeful of the potential of Nexavar in this patient population." Dr. Bruix is coprimary investigator of the phase III trial along with Dr. Josep Llovet, senior scientist of the division of liver disease at Mount Sinai School of Medicine in New York.

Sorafenib Background

In December 2005, sorafenib received approval from the FDA to treat patients with advanced renal cell carcinoma, or kidney cancer. The European Commission has also granted an orphan medicinal product designation for sorafenib in renal cell carcinoma, and a Marketing Authorization Application had been submitted to the European Medicines Agency in September 2005 for treatment of patients with kidney cancer with sorafenib within the European Union.

Sorafenib is the first oral multikinase inhibitor that targets both the tumor cell and tumor vasculature. In preclinical models, sorafenib was shown to target members of two classes of kinases that were known to be involved in both tumor cell proliferation and tumor angiogenesis. These kinases included RAF kinase, VEGFR-2, VEGFR-3, PDGFR-B, KIT, and FLT-3.

Sorafenib is currently in phase III clinical trials for the treatment of liver cancer, metastatic melanoma, or skin cancer, and non-small-cell lung cancer. Overall, the drug has been studied in more than 20 tumor types and in more than 8,000 clinical trial patients. In addition to company-sponsored trials, a variety of sorafenib studies are currently being sponsored by government agencies, cooperative groups, and individual investigators.