NEXAVAR
On The Road To Becoming A Blockbuster
Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals (ONXX) submission of a Supplemental New Drug Application (sNDA) for Nexavar® (sorafenib) tablets is a historical event. It is, indeed, because the drug is intended for a terrible cancer, hepatocellular carcinoma (HCC) that is killing patients with no treatment in the hands of oncologists and with a history of 100 experimental treatments failing to demonstrate safety and efficacy. The drug is already approved for kidney cancer, which is as awful as liver cancer.
Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Death rates from liver cancer continue to increase. HCC is responsible for about 90 percent of the primary liver cancers in adults. It is the fifth most common cancer in the world and the third leading cause of cancer-related deaths globally. Over 600,000 cases of HCC are diagnosed globally each year (about 19,000 in the United States and 32,000 in the European Union and in 2002 approximately 600,000 people (about 13,000 Americans and 57,000 Europeans) died of HCC.
Nexavar is the first drug to demonstrate a significant survival benefit with HCC, and, if approved, it would fulfill a serious unmet need with a manageable toxicity profile.
Why the Submission? The positive data from the international, Phase 3, placebo-controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial. The trial results demonstrated that Nexavar extended overall survival by 44 percent in patients with HCC (HR=0.69; p=0.0006) versus placebo. Side effects are manageable.
Vision: Onyx believes that Nexavar will become the reference standard of care in HCC, and will help advance the firm’s development program. Onyx’ plan includes clinical trials studying Nexavar alone and in combination with other therapies for melanoma, non-small cell lung and breast cancer.
What is Nexavar?
Nexavar is a small molecule drug with dual action. The drug targets both the tumor cell and tumor vasculature. Its targets members are two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) — both contribute to cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET. Preclinical models have demonstrated that Raf/MEK/ERK has a role in HCC; therefore blocking signaling through Raf-1 may offer therapeutic benefits in HCC.
Side effects:
Hypertension may occur early in the course of therapy and blood pressure should be monitored weekly during the first six weeks of therapy and treated as needed.
Incidence of bleeding regardless of causality was 15% for Nexavar vs. 8% for placebo.
Cardiac ischemia/infarction was 2.9% for Nexavar vs. 0.4% for placebo.
Most common adverse events were diarrhea, rash/desquamation, fatigue, hand-foot skin reaction, alopecia, and nausea. Grade 3/4 adverse events were 38% for Nexavar vs. 28% for placebo. Women of child-bearing potential should be advised to avoid becoming pregnant and advised against breast-feeding. In cases of any severe or persistent side effects, temporary treatment interruption, dose modification or permanent discontinuation should be considered.