The US Food and Drug Administration (FDA) has approved Nexavar (sorafenib) tablets, a supplemental NDA (new drug application) for patients with liver cancer (unresectable hepatocellular carcinoma, or HCC). It is the first approved systemic drug therapy for liver cancer, as well as being the only medication therapy proven to significantly improve overall survival in liver cancer patients.

Last month Nexavar was approved in Europe for HCC treatment. The drug is approved in more than 60 countries worldwide. It is the first new treatment for advanced new kidney cancer in over ten years.

Arthur J. Higgins, Chairman of the Executive Committee, Bayer HealthCare, said “The approval of Nexavar in HCC marks the second time in two years that this novel kinase inhibitor has been granted FDA approval on a Priority Review basis, making it rapidly available to patients who previously had limited treatment options. This milestone will likely establish Nexavar as the standard systemic therapy for the treatment of liver cancer and is a turning point in improving treatment outcomes in patients facing the devastating impact of this disease.”

Hollings C. Renton, Chairman/President and CEO, Onyx Pharmaceuticals, Inc., said “Liver cancer is one of the cancers in which the number of related deaths continues to increase “This second approval for Nexavar demonstrates our commitment to expediting the clinical development of this innovative therapy to treat today’s unmet needs in cancer. We are grateful to the patients, families and investigators who make this important research possible.”

HCC accounts for 90% of the primary malignant liver tumors in adults, it is also the most common form of liver cancer. Liver cancer is the third leading cause of cancer-related deaths worldwide, and the sixth most widespread cancer globally. 600,000 people annually are diagnosed with liver cancer worldwide, and its incidence is rising. 19,000 people in the USA, 54,000 in Europe, and 390,000 in China, Korea and Japan are diagnosed with liver cancer each year.

James L. Boyer, M.D., Chairman, American Liver Foundation, said “The American Liver Foundation (ALF) is always pleased when new therapies prove effective for those affected by liver disease. Researchers worldwide, including those supported by ALF, have spent decades studying liver cancer. This new treatment provides a valuable option for liver cancer patients and will enable ALF to further promote the treatment of liver disease through our education and advocacy efforts.”

Positive data from the international Phase III, placebo-controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial demonstrated to the FDA that the drug should be approved. The trial showed that Nexavar gave patients an improved overall survival of 44% (HR=0.69; p=0.0006), compared to a placebo. The median overall survival was 10.7 months for the patients receiving Nexavar, versus 7.9 months for those on the placebo. Imbalances in serious adverse event rates between Nexavar and the placebo groups were not observed. Diarrhea and hand/foot skin reactions were the most common side effects experienced by the Nexavar patients.

Nexavar’s Differentiated Mechanism

Nexavar targets the tumor cell, and tumor vasculature as well. Preclinical studies showed that Nexavar targets members of two classes of kinases which are known to be involved in both cell growth and blood supply (angiogenesis) – two vital processes for cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET. Preclinical models have also shown that Raf/MEK/ERK has a role in HCC. Hence, stopping signaling through Raf-1 may offer therapeutic benefits in HCC.

— www.nexavar.com
— Onyx Pharmaceuticals, Inc.
— Bayer HealthCare

Written by – Christian Nordqvist