Regorafenib is a novel, oral multi-kinase inhibitor that inhibits various signaling pathways responsible for tumor growth. In 2012, we submitted regorafenib for marketing authorization in the treatment of patients with metastatic colorectal cancer (mCRC) in the United States, Europe and Japan. The registration applications are based on the results of the worldwide Phase III CORRECT study. In September 2012, regorafenib was approved in this indication by the U.S. FDA under the trade name Stivarga™. The Japanese Ministry of Health, Labour and Welfare (MHLW) granted priority review status for this substance.

In April 2012, regorafenib reached the primary endpoint – statistically significant extension of progression- free survival – in the Phase III GRID clinical trial. The GRID trial investigated regorafenib in the treatment of patients with metastatic and / or unresectable gastrointestinal stromal tumors (GIST) whose disease had progressed despite prior treatment with imatinib and sunitinib. In August 2012, the substance was submitted for approval in the treatment of GIST in the United States. In October 2012, the U.S. Food and Drug Administration (FDA) granted priority review status to the application. In December 2012, an application for registration was filed with the Japanese MHLW.

In 2011, we signed an agreement with Onyx Pharmaceuticals, Inc., United States, under which Onyx will receive a royalty on any future global sales of regorafenib in oncology.

In a registration-relevant Phase III study (ALSYMPCA), radium-223 dichloride (Alpharadin) – the cancer drug we are jointly developing with Algeta ASA, Norway – demonstrated a significant improvement in overall survival in patients with hormone-refractory prostate cancer (CRPC) and bone metastases. Based on these positive results, we filed registration applications with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for radium-223 dichloride for the treatment of CRPC in December 2012.

In a registration-relevant Phase III study (ALSYMPCA), radium-223 dichloride (Alpharadin) – the cancer drug we are jointly developing with Algeta ASA, Norway – demonstrated a significant improvement in overall survival in patients with hormone-refractory prostate cancer (CRPC) and bone metastases. Based on these positive results, we filed registration applications with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for radium-223 dichloride for the treatment of CRPC in December 2012.

Eylea™ (active ingredient: aflibercept) is our joint developmental project with Regeneron Pharmaceuticals, Inc., United States. Aflibercept blocks the natural growth factor VEGF (vascular endothelial growth factor), thus preventing the abnormal formation of new blood vessels that tend to leak blood. The medication is administered directly into the eye. Regeneron Pharmaceuticals holds exclusive rights in the United States, where Eylea™ has been approved since 2011 for the treatment of wet age-related macular degeneration (AMD). Bayer will market the product outside the United States. In 2012, Eylea™ was approved in various countries, including Japan, Australia and certain Latin American countries, for the treatment of wet AMD. In November 2012, the European Commission granted marketing authorization. The market introduction of Eylea™ in Australia, Japan and Europe began in November 2012.

Sorafinib targets both the tumor cell and tumor vasculature. In preclinical studies, sorafenib has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) – two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.
 
Nexavar™ is currently approved in more than 80 countries for liver cancer and in more than 90 countries for the treatment of patients with advanced kidney cancer. In Europe, Nexavar™ is approved for the treatment of hepatocellular carcinoma and for the treatment of patients with advanced renal cell carcinoma (RCC) who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy. Nexavar™ is also being evaluated by the companies, international study groups, government agencies and individual investigators as a single agent or combination treatment in a wide range of cancers, including lung cancer, thyroid cancer, breast cancer and colorectal cancer.

Xarelto™ (active ingredient: Rivaroxaban) has been used since 2008 for prophylaxis of venous thromboembolism (VTE) in adult patients following elective hip or knee replacement surgery. Xarelto™ is registered in more than 120 countries around the world and marketed in this indication by HealthCare outside the United States. In 2011, Xarelto™ was also approved in the European Union for stroke prevention in patients with atrial fibrillation as well as for the treatment of deep vein thrombosis (DVT) and the prevention of recurring DVT and pulmonary embolism following acute DVT in adult patients. In Japan, Xarelto™ was approved in January 2012 for prophylaxis of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Market introduction began in April 2012.

In the United States, where Xarelto™ has been approved since 2011 for VTE prevention in adult patients following elective hip or knee joint replacement surgery and to reduce the risk of stroke in patients with non-valvular atrial fibrillation, Janssen Pharmaceuticals, Inc., United States – a subsidiary of Johnson & Johnson – holds the commercialization rights for Xarelto™. Bayer HealthCare supports the sales team of Janssen Pharmaceuticals, Inc. in selected hospitals and specialty markets in the United States.