Management Report
9.1 HealthCare
Research and Development
In the first nine months of 2011 we invested €1,442 million in research and development at HealthCare, including €453 million in the third quarter. We have made further progress with our research and development pipeline during the year. (The following description does not include ongoing activities already described in the Annual Report 2010.)
The most important drug candidates currently in the registration process are:
| Products in Registration | [Table 16] |
|---|
| | Indication |
| Qlaira™/Natazia™ (E2V/DNG) | U.S.A., treatment of heavy and/or prolonged menstrual bleeding |
| Valette™ Plus | E.U., oral contraception, combination product with folate |
| VEGF Trap-Eye | Wet age-related macular degeneration |
| Xarelto™ | Stroke prevention in atrial fibrillation |
| Xarelto™ | E.U., treatment and prevention of deep vein thrombosis |
| YAZ™ Flex | E.U., oral contraception, flexible dosage regimen |
The following table shows our most important drug candidates currently in Phase III or II of clinical testing:
| Research and Development Projects (Phases III and II)* | [Table 17] |
|---|
| | Indication | Status |
| Alemtuzumab | Multiple sclerosis | Phase III |
| ATX-101 | Reduction of submental fat | Phase III |
| FC Patch low | Contraception | Phase III |
| Florbetaben | PET imaging in diagnosis of Alzheimer’s disease | Phase III |
| Gadovist™ | Magnetic resonance imaging | Phase III |
| LCS (ULD LNG Contraceptive System) | Contraception | Phase III |
| Nexavar™ | Breast cancer | Phase III |
| Nexavar™ | Thyroid cancer | Phase III |
| Nexavar™ | Non-small-cell lung cancer | Phase III |
Regorafenib (DAST inhibitor)
| Treatment of metastatic or inoperable
gastrointestinal stromal tumors |
Phase III |
| Regorafenib (DAST inhibitor) | Colon cancer | Phase III |
| Riociguat (sGC stimulator) | Pulmonary hypertension (CTEPH) | Phase III |
| Riociguat (sGC stimulator) | Pulmonary hypertension (PAH) | Phase III |
Xarelto™
| Treatment and secondary prevention of venous thromboembolism |
Phase III |
Xarelto™
| Secondary prevention of acute coronary syndrome/myocardial infarction |
Phase III |
| Vaginorm™ | Vulvovaginal atrophy | Phase III |
| VEGF Trap-Eye | Diabetic macular edema | Phase III |
VEGF Trap-Eye
| Abnormal retinal angiogenesis following
pathological myopia |
Phase III |
| VEGF Trap-Eye | Central retinal vein occlusion | Phase III |
| |
| Alpharadin™ | Treatment of bone metastases in breast cancer | Phase II |
| Amikacin Inhale | Pulmonary infection | Phase II |
| BAY 60-4552/vardenafil | Erectile dysfunction | Phase II |
| Ciprofloxacin Inhale | Pulmonary infection | Phase II |
| Mapracorat | Atopic dermatitis | Phase II |
| MEK inhibitor | Cancer | Phase II |
| MR antagonist (BAY94-8862) | Chronic heart failure | Phase II |
| Nexavar™ | Ovarian cancer | Phase II |
| Nexavar™ | Additional indications | Phase II |
| Regorafenib | Cancer | Phase II |
| Riociguat (sGC stimulator) | Pulmonary hypertension | Phase II |
* as of October 20, 2011 PET = positron emission tomography; CTEPH = chronic thromboembolic pulmonary hypertension; PAH = pulmonary arterial hypertension The nature of drug discovery and development is such that not all compounds can be expected to meet the pre-defined project goals. It is possible that any or all of the projects listed above may have to be discontinued due to scientific and/or commercial reasons and will not result in commercialized products. It is also possible that the requisite FDA, European Medicines Agency (EMA) or other regulatory approvals will not be granted for these compounds. |
In April 2011, we submitted a registration application to the Japanese health ministry for our anticoagulant Xarelto™ for stroke prevention in patients with atrial fibrillation.
In a Phase III study (MAGELLAN study) presented in April 2011 on the prevention of venous thromboembolism in hospitalized patients with acute medical illness, Xarelto™ achieved the primary efficacy endpoints. In the first evaluation, however, a consistently positive benefit-risk balance was not seen across the heterogeneous, acutely ill patient population studied. Further analysis is required to identify which patients may derive benefit from thromboprophylaxis with Xarelto™.
In May 2011, a subgroup analysis of the ROCKET AF Phase III clinical study confirmed that Xarelto™ is highly effective in the prevention of recurrent strokes in patients with atrial fibrillation who have experienced a prior stroke or transient ischemic attack.
At the beginning of July 2011, the U.S. Food and Drug Administration (FDA) approved Xarelto™ for the prevention of deep vein thrombosis (DVT) in people undergoing knee or hip replacement surgery.
In July 2011, a study conducted exclusively in Japan, the Phase III J-ROCKET AF study of Xarelto™ in patients with non-valvular atrial fibrillation at risk of stroke, met its primary endpoint, demonstrating non-inferiority versus warfarin for the principal safety outcome – the composite of major and non-major clinically relevant bleeding.
In September 2011, the Cardiovascular and Renal Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) recommended approval of Xarelto™ for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in the United States. A decision by the FDA is expected in early November 2011.
In September 2011 we received from the European Committee for Medicinal Products for Human Use (CHMP) a recommendation for the registration of Xarelto™ in two new indications: prevention of stroke in adult patients with atrial fibrillation, and treatment of deep vein thrombosis (DVT) and prevention of recurrent DVT and pulmonary embolism (PE) in adults. The decision of the European Commission is expected in the fourth quarter of 2011.
In September 2011 the double-blind, placebo-controlled Phase III ATLAS ACS TIMI 51 clinical trial of Xarelto™ plus standard therapy met its primary efficacy endpoint, showing a statistically significant reduction in the rate of events for the primary composite endpoint of cardiovascular death, myocardial infarction and stroke in patients with acute coronary syndrome, compared to standard therapy plus placebo. For the primary safety endpoint, defined as major bleeding events according to the TIMI classification that are not associated with coronary artery bypass graft surgery, there was a statistically significant increase in such events in patients receiving rivaroxaban versus placebo.
Together with our cooperation partner Regeneron Pharmaceuticals, Inc., United States, we launched the first of two Phase III studies with the clinical development product VEGF Trap-Eye in patients with diabetic macular edema (DME) in April 2011. VEGF Trap-Eye also demonstrated positive results in a second Phase III study in patients with macular edema due to central retinal vein occlusion.
In addition, in June 2011 we submitted applications to both the European Medicines Agency (EMA) and the Japanese Ministry of Health for registration of VEGF Trap-Eye to treat wet age-related macular degeneration (wet AMD).
In a Phase III study, Alpharadin™ – the cancer drug we are jointly developing with Algeta ASA, Norway – demonstrated a significant improvement in overall survival in patients with castration-resistant prostate cancer and bone metastases. With the positive efficacy data, the study met its primary endpoint and was concluded ahead of schedule in June 2011. We are now evaluating the filing strategy for Alpharadin™ based on the recommendation of the Independent Data Monitoring Committee (IDMC) that this study be concluded ahead of schedule.
In August 2011 the cancer drug Alpharadin™ was granted fast-track designation by the U.S. Food and Drug Administration (FDA) for the treatment of castration-resistant prostate cancer in patients with bone metastases.
In May 2011, the cancer drug Nexavar™, developed in cooperation with Onyx Pharmaceuticals, Inc., United States, also achieved positive study results in breast cancer. In a Phase IIb study in patients with locally advanced or metastatic breast cancer, Nexavar™ in combination with chemotherapy (gemcitabine or capecitabine) showed statistically significant improvements in progression-free survival and time-to-progression.
In May 2011, the U.S. Food and Drug Administration (FDA) granted fast-track designation to regorafenib for the therapy of metastatic and/or inoperable gastrointestinal stromal tumors.
May 2011 also saw the presentation of a successful Phase II study with riociguat in pulmonary hypertension owing to chronic obstructive pulmonary disease (COPD).
The U.S. Food and Drug Administration (FDA) granted marketing authorization in March 2011 for Gadavist™ as a contrast agent for magnetic resonance imaging of the central nervous system. Gadavist™ is known under the brand name Gadovist™ outside the United States and is marketed in more than 60 countries worldwide.
In April 2011, we received marketing authorization from the European Commission for the companion animal products Veraflox™ (active ingredient: pradofloxacin) and Procox™ (active ingredients: emodepside and toltrazuril). Veraflox™ is the first next-generation fluoroquinolone antibiotic for the treatment of bacterial infections in cats and dogs. Procox™ is the first combination treatment for roundworm and coccidia in dogs.
In May 2011 we launched Advanced Aspirin™, a formulation of our pain reliever with particularly rapid action, in the United States.
Capital expenditures, acquisitions and cooperations
In January 2011, Bayer acquired the New Zealand company Bomac, which offers a wide range of animal health products for the livestock sector. We plan to introduce the products outside of Australia and New Zealand as well, particularly in emerging markets.
In February 2011, we formed the joint venture Bayer Zydus Pharma in India together with the Indian company Zydus Cadila. With this sales and marketing company, we aim to greatly strengthen our presence in India’s rapidly expanding pharmaceutical market. We hold 50% of the shares of Bayer Zydus Pharma.
In July 2011 we signed an exclusive agreement with Trius Therapeutics, Inc., United States, to jointly develop and commercialize Trius’ antibiotic tedizolid phosphate (tedizolid). The agreement gives us exclusive rights for the markets of Asia – excluding North and South Korea – and all countries of Africa, Latin America and the Middle East. According to the agreement, we will develop tedizolid, which is already in Phase III clinical development in the United States and Europe, for the treatment of various infectious diseases, such as acute bacterial skin and skin structure infections and Gram-positive pneumonia. Trius retains full development and commercialization rights for the United States, Canada and the European Union.
In September 2011 we acquired U.S.-based Pathway Medical Technologies, Inc., a leading supplier of products to mechanically remove arterial plaques. This acquisition expands our presence in the field of interventional cardiology and thus strengthens the MEDRAD Interventional business unit.
In 2011, we plan to invest €44 million in new research and production facilities at the Wuppertal site, including the expansion of production capacities for Xarelto™ and Glucobay™.
Emerging markets
In the emerging markets, HealthCare increased sales by 10.5% (Fx adj.) in the first nine months of 2011 to €3,988 million, including €1,369 million (Fx adj. +8.3%) in the third quarter. The strongest growth was recorded in China. In line with our growth strategy, we raised sales there by 13.6% (Fx adj.) through increased marketing activities, especially the expansion of our distribution network. Business also developed well in the Latin America region, with sales gains in Brazil, Mexico, Venezuela and Argentina, particularly for pharmaceuticals. The emerging markets’ share of total HealthCare sales in the first nine months and the third quarter of 2011 was 31.7% and 32.6%, respectively.