Over 1,000 Medical Sites in the United States Now Licensed to Administer Xofigo® (radium Ra 223 dichloride) Injection

WHIPPANY, N.J., Aug. 13, 2014 /PRNewswire/ -- Bayer HealthCare Inc. today announced that, approximately one year following the national launch, over 1,000 sites in the United States have received the appropriate licensing from the U.S. Nuclear Regulatory Commission (NRC) or appropriate Agreement State to administer Xofigo^® (radium Ra 223 dichloride) injection, an alpha particle-emitting radioactive therapeutic agent indicated for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastatic disease.¹

Since the U.S. Food and Drug Administration approval of Xofigo in May 2013, Bayer has worked with medical sites around the country to apply for and confirm existing NRC or appropriate Agreement State licensing to administer Xofigo.

"Xofigo is now available within a 50-mile travel radius to 96 percent of the indicated patient population in the U.S.," said Joseph Germino, M.D., Vice President of Medical Affairs, Oncology, Bayer HealthCare. "We will continue to work with unlicensed sites to secure authorization to administer Xofigo, ensuring all patients who may benefit from this treatment have access. We are proud to reach this milestone and extend our appreciation to all providers of Xofigo for their hard work and ceaseless dedication to their patients who need this therapy."

To date, thousands of patients have received Xofigo at cancer treatment centers across the country, including top prescribing sites: 

• Associated Medical Professionals, Syracuse, New York
• Carolinas HealthCare System's Carolinas Medical Center, Charlotte, North Carolina
• Cleveland Clinic Nuclear Medicine, Cleveland, Ohio
• Dana Farber Cancer Institute, Boston, Massachusetts
• Memorial Sloan Kettering Cancer Center, New York, New York
• Moffitt Cancer Center, Tampa, Florida
• The University of Texas MD Anderson Cancer Center, Houston, Texas
• Urology Cancer Center, Omaha, Nebraska

Xofigo is the first and only FDA-approved alpha particle-emitting radioactive therapeutic agent with an anti-tumor effect on bone metastases that has also demonstrated an improvement in overall survival compared to placebo, as shown in the pivotal Phase III ALSYMPCA trial; median overall survival (OS) was 14.0 months with Xofigo plus best standard of care (95% CI 12.1-15.8) vs. 11.2 months with placebo plus best standard of care (95% CI 9.0-13.2) [HR=0.695 (95% CI 0.552-0.875), p=0.00185]. Xofigo also delayed time to first symptomatic skeletal event (SSE) compared to placebo. The majority of events consisted of external beam radiation therapy (EBRT) to bone metastases to relieve skeletal symptoms.

Bone is the most common site in the body to be affected by metastatic cancer, and bone metastases are particularly prevalent in patients with metastatic prostate cancer.² Ninety percent of all men with mCRPC have radiological evidence of bone metastases, which can lead to an increase in frequency of skeletal events.^3-6

About Xofigo^® (radium Ra 223 dichloride) Injection
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 Ra 223 dichloride is less than 100 micrometers which may limit the damage to the surrounding normal tissue.¹

Important Safety Information for Xofigo^® (radium Ra 223 dichloride) Injection

• Contraindications: Xofigo is contraindicated in women who are or may become pregnant. Xofigo can cause fetal harm when administered to a pregnant woman.
• Bone Marrow Suppression: 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 leucopenia – 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.
• Hematological Evaluation: 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.
• Concomitant Use with Chemotherapy: 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.
• Administration and Radiation Protection: 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.
• Fluid Status: Dehydration occurred in 3% of patients on Xofigo and 1% of patients on placebo. Xofigo increases adverse reactions such as diarrhea, nausea, and vomiting, which may result in dehydration. Monitor patients' oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of dehydration or hypovolemia.
• Injection Site Reactions: Erythema, pain, and edema at the injection site were reported in 1% of patients on Xofigo.
• Secondary Malignant Neoplasms: Xofigo contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects. Due to its mechanism of action and neoplastic changes, including osteosarcomas, in rats following administration of radium -223 dichloride, Xofigo may increase the risk of osteosarcoma or other secondary malignant neoplasms. However, the overall incidence of new malignancies in the randomized trial was lower on the Xofigo arm compared to placebo (<1% vs 2%; respectively), but the expected latency period for the development of secondary malignancies exceeds the duration of follow up for patients on the trial.
• Subsequent Treatment with Cytotoxic Chemotherapy: In the randomized clinical trial, 16% patients in the Xofigo group and 18% patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with Xofigo will tolerate subsequent cytotoxic chemotherapy.
• Adverse Reactions: The most common adverse reactions (³10%) 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 (³10%) 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 http://labeling.bayerhealthcare.com/html/products/pi/Xofigo_PI.pdf.

Please visit the Xofigo Facility Finder, available at http://xofigo-us.com/hcp/facility-finder/, to find a treatment center licensed to administer Xofigo.

About Castration-Resistant Prostate Cancer (CRPC) and Bone Metastases
Prostate cancer is the most common cancer among men in the United States (other than skin cancer).⁷ Approximately four percent of prostate cancer cases are considered distant, which means that the cancer has spread beyond the prostate to distant areas of the body (metastasized).⁸ If prostate cancer starts to spread to other areas of the body, it most commonly goes to the bone.⁹ Once the cancer has reached the bone, interactions between tumors cells and the bone cells responsible for breaking down and rebuilding bone result in excessive bone rebuilding and rapid tumor growth.⁸

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 Pharmaceuticals Inc. 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.

© 2014 Bayer HealthCare Pharmaceuticals Inc.
BAYER, 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. Coleman R. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27:165-176.
3. Supplementary appendix to Scher HI, Fizazi K, Saad F, et al; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367 (13):1187-1197.
4. Fizazi K, Scher HI, Molina A, et al; COU-AA-301Investigators. 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 [published correction appears in Lancet Oncol. 2012;13(11):e464] Lancet Oncol. 2012;13(10):983-992.
5. Tannock IF, de Wit R, Berry WR, et al; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502-1512.
6. Petrylak DP, Tangen CM, Hussain MHA, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513-1520.
7. National Cancer Institute, Surveillance Epidemiology and End Results (SEER). SEER Stat Facts: Prostate; Survival & Stage, 2002-2008.
8. Jin, Dayyani, and Gallick. Steps in Prostate Progression that Lead to Bone Metastasis. International Journal of Cancer. 2011.
9. American Cancer Society. Prostate Cancer: Detailed Guide. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003134-pdf.pdf

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