Bayer HealthCare Pharmaceuticals
Focus on therapeutic areas with a high medical need
Improving patients' quality of life with innovations
We conducted clinical studies with several drug candidates from our research and development pipeline during 2012 to drive the development of new substances to treat diseases with a high unmet medical need. Following the completion of the required studies with a number of these drug candidates, we submitted applications to one or more regulatory agencies for approvals or approval extensions.
Four active ingredients / products have blockbuster potential. Of special importance is our anticoagulant Xarelto™ (rivaroxaban), which continues to be launched in more countries. In 2012 we filed for, and in some cases already received, marketing authorization in additional indications.
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.
Based on the successful EINSTEIN-PE study, we submitted an application to the European Medicines Agency (EMA) in April 2012 for marketing authorization of Xarelto™ in the treatment of pulmonary embolism and the secondary prevention of recurrent deep vein thrombosis and pulmonary embolism. We were granted marketing authorization in November 2012. In May 2012, our cooperation partner Janssen Research & Development, LLC, United States, submitted applications to the U.S. Food and Drug Administration (FDA) seeking approval for Xarelto™ in the treatment of deep vein thrombosis or pulmonary embolism and in secondary prevention of recurrent venous thromboembolism (VTE). In November 2012, the FDA granted marketing authority for these applications following a priority review. In December 2011, we submitted an application to the EMA for marketing authorization for Xarelto™ (rivaroxaban) in secondary prevention following acute coronary syndrome (ACS). The application for marketing approval in this indication in the U.S. was submitted to the FDA by our cooperation partner Janssen Research & Development, LLC. In June 2012, we received a Complete Response Letter from the FDA regarding the ACS indication. The requested information was submitted in September 2012 by our cooperation partner Janssen Research & Development, LLC. The application for Xarelto™ in the prevention of stent thrombosis in patients with acute coronary syndrome was submitted at the same time. The European application for marketing authorization for secondary prevention after acute coronary syndrome also includes prevention of stent thrombosis.
In the area of oncology, regorafenib (registered in the United States under the trademark Stivarga™) is approved for the treatment of advanced colorectal cancer in some countries, and approval is pending in others. At the end of 2012, we filed for marketing authorization for radium-223 dichloride (Alpharadin) for the therapy of bone metastases in prostate cancer patients.
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.
Another example is our cancer drug Nexavar™ (active ingredient: sorafenib), which we are continuing to develop jointly with Onyx Pharmaceuticals, Inc., United States. The successful active substance sorafenib, which attacks both cancer cells and the vascular system of the tumor, has been registered for the treatment of advanced renal cell carcinoma since 2005 and for hepatocellular carcinoma since 2007. We plan to develop the product beyond these two therapeutic areas with a broadly based lifecycle management program. In January 2013, a Phase III clinical trial investigating sorafenib as a monotherapy in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory differentiated thyroid cancer met its primary endpoint of a statistically significant improvement in progression-free survival. Based on these data, we plan to apply for marketing authorization for sorafenib in the treatment of RAI-refractory differentiated thyroid cancer. Sorafenib is also being investigated in Phase III registration studies as an adjuvant therapy following curative tumor resection in patients with renal cell carcinoma and hepatocellular carcinoma. We are also conducting Phase III studies in breast cancer. Two Phase III clinical trials with sorafenib did not show the desired results: a study in patients with advanced non-small-cell lung cancer whose disease had progressed after two or three previous treatments and a combination study with sorafenib and erlotinib in liver cancer did not meet their primary endpoints.
Other promising products being launched include Eylea™ (aflibercept) for the treatment of wet age-related macular degeneration.
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.
We regularly evaluate our research and development pipeline in order to prioritize the most promising pharmaceutical projects.
Riociguat is the first member of a new class of vasodilating agents known as soluble guanylate cyclase (sGC) stimulators. Administered in tablet form, riociguat is currently being investigated as a new approach for the treatment of various forms of pulmonary hypertension. The registration-relevant Phase III CHEST-1 and PATENT-1 studies each reached their primary endpoints in October 2012. In both studies, the substance demonstrated a statistically significant improvement in physical fitness among patients with chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH) compared with placebo. Based on these studies, we submitted riociguat in February 2013 for marketing approval in the United States and the European Union for the treatment of CTEPH and PAH.
In the area of women’s healthcare, we are conducting research into gynecological therapies and additional contraception options. FC-Patch Low (ethinylestradiol / gestodene) is intended to become the only transparent product of its kind and the smallest, lowest-dosed contraceptive patch on the market. In September 2012, we applied for marketing authorization for this product in the European Union. In December 2012, the European registration process for our new, low-dose hormone-releasing intrauterine device LCS-12 was successfully concluded. This device is smaller than Mirena™ and has a duration of use of up to three years. We plan to market this new contraceptive coil in the European Union under the brand name “Jaydess.”
In January 2013, LCS-12 received approval in the United States under the trademark Skyla™. A further, also small hormone-releasing device (LCS-16), with a duration of use of up to five years, is currently in Phase III clinical development. In October 2012, the European Commission authorized the approval of our new low-dose combined oral contraceptive Flexyess™ (drospirenone / ethinylestradiol). The flexible extended regimen enables users to choose the number and timing of their periods according to their needs. First launches of the product are expected in the second half of 2013.
We also invest in continuous life-cycle management to identify possible additional indications and improved delivery forms for products already on the market. For example, the additional indication for our oral contraceptive Qlaira™/ Natazia™ – treatment of heavy and / or prolonged menstrual bleeding not caused by any diagnosed conditions of the uterus – was approved in the United States in March 2012.