WHIPPANY, N.J., Nov. 30, 2017 /PRNewswire/ -- Bayer today announced that an Independent Data Monitoring Committee (IDMC) has recommended to unblind a Phase III trial of radium Ra 223 dichloride (radium-223) in combination with abiraterone acetate and prednisone/prednisolone in prostate cancer. The IDMC recommendation is due to the observation of an imbalance of more fractures and deaths in the treatment arm investigating radium-223 in combination with abiraterone and prednisone/prednisolone in patients with asymptomatic or mildly symptomatic, chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Bayer is now unblinding the study per the IDMC's recommendation and will thoroughly analyze the findings and continue monitoring as per study protocol. Data from other types of studies in which this combination treatment was evaluated did not show new safety signals.

"Patient safety is our top priority. We are therefore unblinding the study to thoroughly analyze the data," said Mike Devoy, Member of the Pharmaceuticals' Division Executive Committee and Chief Medical Officer at Bayer. "It is important to note that, based on available data from previous trials as well as real-world use, the benefit-risk profile of Xofigo in its approved indication remains favorable. We remain committed to further exploring the potential of radium-223 across multiple tumor types with significant unmet medical need, including prostate cancer."

This Phase III trial evaluates the investigational use of radium Ra 223 dichloride in combination with abiraterone acetate and prednisone/prednisolone compared to placebo plus abiraterone acetate and prednisone/prednisolone in patients with asymptomatic or mildly symptomatic chemotherapy-naïve bone predominant metastatic castration-resistant prostate cancer (CRPC). The primary endpoint of the trial is symptomatic skeletal event-free survival (SSE-FS). The trial completed enrollment in September 2016, therefore no patients in the combination arm are receiving radium Ra 223 dichloride which is only administered for up to 6 doses (one dose every 4 weeks).

Bayer has informed relevant health authorities regarding the study unblinding as well as investigators of trials with radium Ra 223 dichloride and is preparing the respective information for healthcare professionals. In addition, the company is in the process of gathering the detailed study findings and will update health authorities and healthcare professionals accordingly.

For further information, patients should contact their healthcare professionals.

Since its approval in 2013, more than 18,000 U.S. patients¹ have been treated with radium-223. The benefit-risk profile demonstrated in the Phase III ALSYMPCA trial which resulted in the approval of Xofigo remains favorable.

Phase III Trial Design
The randomized double-blind, placebo-controlled Phase III trial ERA223 was designed to investigate whether providing radium Ra 223 dichloride (radium-223) in combination with abiraterone acetate and prednisone/prednisolone will extend symptomatic skeletal event free survival (SSE-FS). The trial has enrolled 806 patients who were randomized in a 1:1 ratio to receive either study treatment of radium-223 dichloride for six cycles with abiraterone acetate plus prednisone/prednisolone or placebo for six cycles with abiraterone acetate plus prednisone/prednisolone and best supportive care. Patients in both arms were scheduled to receive treatment with abiraterone acetate plus prednisone/prednisolone until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met). For further information about the study, please visit www.clinicaltrials.gov.

About Castration-Resistant Prostate Cancer (CRPC) and Bone Metastases
The stage of prostate cancer is one of the most important factors in determining treatment options and the outlook for recovery. If prostate cancer spreads, or metastasizes, beyond the prostate gland, it often first grows into nearby tissues or lymph nodes before spreading to the bones.

CRPC is an advanced form of prostate cancer. Approximately nine in 10 patients with CRPC (90 percent) develop bone metastases, impacting survival. In fact, bone metastases lead to an increased risk of death in patients with CRPC. Therefore, diagnosing and treating bone metastases at the earliest onset is critical for patients.

About Xofigo^® (radium Ra 223 dichloride) Injection
Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.²

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 (≥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 (≥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 http://labeling.bayerhealthcare.com/html/products/pi/Xofigo_PI.pdf.

Bayer: Science For A Better Life
Bayer is a global enterprise with core competencies in the Life Science fields of health care and agriculture. Its products and services are designed to benefit people and improve their quality of life. At the same time, the Group aims to create value through innovation, growth and high earning power. Bayer is committed to the principles of sustainable development and to its social and ethical responsibilities as a corporate citizen. In fiscal 2016, the Group employed around 115,200 people and had sales of EUR 46.8 billion. Capital expenditures amounted to EUR 2.6 billion, R&D expenses to EUR 4.7 billion. These figures include those for the high-tech polymers business, which was floated on the stock market as an independent company named Covestro on October 6, 2015. For more information, go to www.bayer.us.

© 2017 Bayer
BAYER, the Bayer Cross and Xofigo are registered trademarks of Bayer.

Contact:
Rose Talarico, phone +862.404.5302
Email: rose.talarico@bayer.com

Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer 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      Cardinal Health New Patient Data.  Accessed November 2017
2      XOFIGO^® (radium Ra 223 dichloride) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, May 2017.

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Intended for U.S. Media

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