Xofigo® (radium Ra 223 dichloride) Injection Recommended for Approval in the European Union

WHIPPANY, N.J., Sept. 20, 2013 /PRNewswire/ -- Bayer HealthCare announced today that the the European Committee for Medicinal Products for Human Use (CHMP) recommended Xofigo^® (radium Ra 223 dichloride) for approval with a proposed indication for the treatment of adults with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastases. The decision of the European Commission on the approval is expected in the second half of 2013. Xofigo was approved by the U.S. Food and Drug Administration in May for the treatment of patients with CRPC, symptomatic bone metastases and no known visceral metastatic disease and is now available in the United States at licensed facilities.¹

"We are encouraged by the positive CHMP opinion issued today, and look forward to potentially providing radium 223 to more patients upon approval of the European Commission," explained Kemal Malik, MD, Member of the Bayer HealthCare Executive Committee and Head of Global Development.

About Xofigo^® (radium Ra 223 dichloride) Injection
Xofigo is indicated in the United States for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.¹

Xofigo is an alpha particle-emitting radioactive therapeutic agent with an anti-tumor effect on bone metastases. The active ingredient in Xofigo is the alpha particle-emitting isotope radium-223, which mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The high linear energy transfer of Xofigo may cause double-strand DNA breaks in adjacent cells, resulting in an anti-tumor effect on bone metastases. The alpha particle range from radium-223 dichloride is less than 100 micrometers which may limit the damage to the surrounding normal tissue.¹

In September 2009, Bayer signed an agreement with Algeta ASA (Oslo, Norway) for the development and commercialization of Xofigo. Under the terms of the agreement, Bayer will develop, apply for health authority approvals worldwide and commercialize Xofigo globally. Algeta US, LLC is co-promoting Xofigo with Bayer in the US.

Important Safety Information for Xofigo^® (radium Ra 223 dichloride) Injection
Xofigo is contraindicated in women who are or may become pregnant. Xofigo can cause fetal harm when administered to a pregnant woman.

In the randomized trial, 2% of patients in the Xofigo arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with Xofigo bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the Xofigo arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (<1%) was similar for patients treated with Xofigo and placebo. Myelosuppression –notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia– has been reported in patients treated with Xofigo.

Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for bone marrow failure.

Monitor blood counts at baseline and prior to every dose of Xofigo. Prior to first administering Xofigo, the absolute neutrophil count (ANC) should be greater than or equal to 1.5 × 10⁹/L, the platelet count greater than or equal to 100 × 10⁹/L, and hemoglobin greater than or equal to 10 g/dL. Prior to subsequent administrations, the ANC should be greater than or equal to 1 × 10⁹/L and the platelet count greater than or equal to 50 × 10⁹/L. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care.

Safety and efficacy of concomitant chemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use of Xofigo in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued.

Xofigo should be received, used, and administered only by authorized persons in designated clinical settings. The administration of Xofigo is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations.

The most common adverse reactions (greater than or equal to 10%) in the Xofigo arm vs the placebo arm, respectively, were nausea (36% vs 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheral edema (13% vs 10%). Grade 3 and 4 adverse events were reported in 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in the Xofigo arm (greater than or equal to 10%) vs the placebo arm, respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs 53%), leukopenia (35% vs 10%), thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%).

For full prescribing information visit www.xofigo-us.com. 

About CRPC and Bone Metastases
Prostate cancer is the most common cancer among men in the United States (other than skin cancer).³ Approximately 4% of prostate cancer cases are considered distant, which means that the cancer has spread beyond the prostate to distant areas of the body (metastasized).⁴ If prostate cancer starts to spread to other areas of the body, it most commonly goes to the bone.³

Bone is the most common site in the body to be affected by metastatic cancer, and bone metastases are particularly prevalent in patients with prostate cancer.⁵  Approximately 90% of patients with metastatic prostate cancer show evidence of bone metastases.^6,7,8,9 Bone metastases can lead to an increase in frequency of skeletal events and are shown to be the main cause of death in patients with CRPC.^10,11

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now includes three oncology products and several other compounds in various stages of clinical development. Together, these products reflect the company's approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

About Bayer HealthCare Pharmaceuticals Inc.
Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare is one of the world's leading, innovative companies in the healthcare and medical products industry, and combines the activities of the Animal Health, Consumer Care, Medical Care, and Pharmaceuticals divisions.  As a specialty pharmaceutical company, Bayer HealthCare provides products for General Medicine, Hematology, Neurology, Oncology and Women's Healthcare.  The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

Bayer^® and the Bayer Cross^® and Xofigo^® are registered trademarks of Bayer.

Forward-Looking Statement
This news release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

¹   XOFIGO^® (radium Ra 223 dichloride) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, May 2013. 

²  Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213-23.

³   American Cancer Society. Prostate Cancer: Detailed Guide. Available at:     http://www.cancer.org/acs/groups/cid/documents/webcontent/003134-pdf.pdf

⁴   National Cancer Institute, Surveillance Epidemiology and End Results (SEER). SEER Stat Facts: Prostate; Survival & Stage, 2002-2008.

⁵   Coleman R. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27:165-176.

⁶   Petrylak DP, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513-1520.

⁷   Tannock IF, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502-1512.

⁸   Scher, HI, et al. Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy. N Engl J Med. 2012;DOI10.1056

⁹   Fizazi, K, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2012; 13:983-92.

¹⁰  Saad, MD, et. al. "Guidelines for the management of castration-resistant prostate cancer." Can Urol Assoc J    2010;4(6):380-4.

¹¹  Lange PH, Vasella RL. Mechanisms, hypotheses and questions regarding prostate cancer metastatic to bone. Cancer & Metastasis Reviews.1999;17:331-336.

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SOURCE Bayer HealthCare Pharmaceuticals Inc.