AMGN Amgen Inc

WHIPPANY, N.J., Sept. 14, 2015 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals Inc. announced today that data from its growing oncology portfolio will be presented at the 2015 European Cancer Congress (ECC2015), September 25 - 29, in Vienna, Austria. These data include further analyses from the CONSIGN and CONCUR trials of Stivarga^® (regorafenib) tablets in previously treated metastatic colorectal cancer (mCRC) patients, and findings from the Phase III ALSYMPCA trial and the U.S. expanded access program (EAP) of Xofigo^® (radium Ra 223 dichloride) injection in patients with metastatic castration-resistant prostate cancer (mCRPC), symptomatic bone metastases and no known visceral metastatic disease.

In addition, Bayer will present early clinical findings on its investigational compound, roniciclib (BAY-1000394), a cyclin-dependent kinase (CDK) inhibitor currently in Phase II clinical development as a first-line therapy in combination with chemotherapy for extensive disease small cell lung cancer (ED-SCLC).

"Building on the clinical success of our approved oncology portfolio, we continue to prioritize the treatment development programs that show promise for combating the toughest cancers with high unmet medical needs," said Joerg Moeller, M.D., member of Bayer's HealthCare Executive Committee and head of Global Development. "The research Bayer is presenting at ECC2015 represents our ongoing commitment to advancing our understanding of therapeutic options for cancer patients worldwide."

Notable studies evaluating products and compounds from Bayer at ECC2015 are listed below:

Radium Ra 223 Dichloride (radium-223)

• Baseline characteristics, number of radium-223 dichloride injections, and overall survival (OS) in US Expanded Access Program (EAP) and ALSYMPCA
  • Abstract #2530, Board P021, Poster Session: Genitourinary Malignancies (Hall C)
  • September 28, 2015 at 4:45PM – 6:45PM (CEST)
• 3-year follow-up of chemotherapy following radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients (pts) with symptomatic bone metastases (mets) from ALSYMPCA
  • Abstract #2510, Poster Discussion Session: Genitourinary Malignancies (Hall C2)
  • September 28, 2015 at 8:00AM – 9:00AM (CEST)
  • Abstract #2510, Board P001, Poster Session: Genitourinary Malignancies (Hall C)
  • September 28, 2015 at 4:45PM – 6:45PM (CEST)
• Effects of concomitant use of abiraterone and/or enzalutamide with radium-223 on safety and overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients treated in an international early access program (EAP)
  • Abstract #2561, Board P052, Poster Session: Genitourinary Malignancies – Prostate Cancer (Hall C)
  • September 28, 2015 at 4:45PM – 6:45PM (CEST)
• Experience with radium-223 as a systemic treatment for patients (pts) with castration-resistant prostate cancer (CRPC) out of a clinical trial in Spain
  • Abstract #2540, Board P031, Poster Session: Genitourinary Malignancies – Prostate Cancer (Hall C)
  • September 28, 2015 at 4:45PM – 6:45PM (CEST)

Regorafenib

mCRC

• Regorafenib for previously treated metastatic colorectal cancer (mCRC): Results from 683 Italian patients treated in the open-label phase 3B CONSIGN study
  • Abstract #2143, Board P133, Poster Session: Gastrointestinal Malignancies – Colorectal Cancer (Hall C)
  • September 27, 2015 at 9:15 AM – 11:15 AM (CEST)
• CONSIGN: An open-label phase 3B study of regorafenib in patients with metastatic colorectal cancer (mCRC) who failed standard therapy
  • Abstract #2139, Board P129, Poster Session: Gastrointestinal Malignancies – Colorectal Cancer (Hall C)
  • September 27, 2015 at 9:15 AM – 11:15 AM (CEST)
• Analysis of biomarkers in circulating tumor DNA from the phase 3 CONCUR study of regorafenib in Asian patients with metastatic colorectal cancer (mCRC): Correlation with clinical outcome
  • Abstract #2013, Poster Discussion Session: Gastrointestinal Malignancies – Colorectal Cancer (Hall A1)
  • September 27, 2015 at 8:00 AM – 9:00 AM (CEST)
  • Abstract #2013, Board P003, Poster Session: Gastrointestinal Malignancies – Colorectal Cancer (Hall C)
  • September 27, 2015 at 9:15 AM – 11:15 AM (CEST)

Gastrointestinal stromal tumour (GIST)

• Tumor genotyping and clonal evolution in KIT during regorafenib treatment in the phase III GRID study of regorafenib vs placebo in tyrosine kinase inhibitor (TKI)-refractory GIST
  • Abstract #2341, Board P303, Poster Session: Gastrointestinal Malignancies –Noncolorectal Cancer (Hall C)
  • September 28, 2015 at 9:15 AM – 11:15 AM (CEST)

Pipeline

• Phase Ib/II study of the CDK inhibitor roniciclib (BAY-1000394) in combination with chemotherapy as first-line therapy in subjects with extensive disease in small-cell lung cancer
  • Abstract #3100, Board P352, Poster Session: Lung Cancer - Metastatic Disease
    (Hall C)
  • September 27, 2015 at 9:15 AM – 11:15 AM (CEST)

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.

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 (>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.

About Stivarga (regorafenib)
In the United States, Stivarga is indicated for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. It is also indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.²

Stivarga is an inhibitor of multiple kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis and maintenance of the tumor microenvironment.²

Stivarga is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx Pharmaceuticals, Inc., an Amgen subsidiary (NASDAQ: AMGN), under which Onyx receives a royalty on all global net sales of Stivarga in oncology.

Important Safety Information for Stivarga^® (regorafenib) tablets:

WARNING: HEPATOTOXICITY

• Severe and sometimes fatal hepatotoxicity has been observed in clinical trials.
• Monitor hepatic function prior to and during treatment.
• Interrupt and then reduce or discontinue Stivarga for hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis, depending upon severity and persistence.

Hepatotoxicity: Severe drug-induced liver injury with fatal outcome occurred in 0.3% of 1200 Stivarga-treated patients across all clinical trials. In metastatic colorectal cancer (mCRC), fatal hepatic failure occurred in 1.6% of patients in the Stivarga arm and in 0.4% of patients in the placebo arm; all the patients with hepatic failure had metastatic disease in the liver. In gastrointestinal stromal tumor (GIST), fatal hepatic failure occurred in 0.8% of patients in the Stivarga arm.

Liver Function Monitoring: Obtain liver function tests (ALT, AST, and bilirubin) before initiation of Stivarga and monitor at least every 2 weeks during the first 2 months of treatment. Thereafter, monitor monthly or more frequently as clinically indicated. Monitor liver function tests weekly in patients experiencing elevated liver function tests until improvement to less than 3 times the upper limit of normal (ULN) or baseline values. Temporarily hold and then reduce or permanently discontinue Stivarga, depending on the severity and persistence of hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis.

Hemorrhage: Stivarga caused an increased incidence of hemorrhage. The overall incidence (Grades 1-5) was 21% and 11% with Stivarga vs 8% and 3% with placebo in mCRC and GIST patients, respectively. Fatal hemorrhage occurred in 4 of 632 (0.6%) Stivarga-treated patients and involved the respiratory, gastrointestinal, or genitourinary tracts. Permanently discontinue Stivarga in patients with severe or life-threatening hemorrhage and monitor INR levels more frequently in patients receiving warfarin.

Dermatological Toxicity: Stivarga caused an increased incidence of hand-foot skin reaction (HFSR) (also known as palmar-plantar erythrodysesthesia [PPE]) and severe rash, frequently requiring dose modification. The overall incidence was 45% and 67% with Stivarga vs 7% and 12% with placebo in mCRC and GIST patients, respectively. Incidence of Grade 3 HFSR (17% vs 0% in mCRC and 22% vs 0% in GIST), Grade 3 rash (6% vs <1% in mCRC and 7% vs 0% in GIST), serious adverse reactions of erythema multiforme (0.2% vs 0% in mCRC), and Stevens-Johnson syndrome (0.2% vs 0% in mCRC) was higher in Stivarga-treated patients. Toxic epidermal necrolysis occurred in 0.17% of 1200 Stivarga-treated patients across all clinical trials. Withhold Stivarga, reduce the dose, or permanently discontinue depending on the severity and persistence of dermatologic toxicity.

Hypertension: Stivarga caused an increased incidence of hypertension (30% vs 8% in mCRC and 59% vs 27% in GIST with Stivarga vs placebo, respectively). Hypertensive crisis occurred in 0.25% of 1200 Stivarga-treated patients across all clinical trials. Do not initiate Stivarga until blood pressure is adequately controlled. Monitor blood pressure weekly for the first 6 weeks of treatment and then every cycle, or more frequently, as clinically indicated. Temporarily or permanently withhold Stivarga for severe or uncontrolled hypertension.

Cardiac Ischemia and Infarction: Stivarga increased the incidence of myocardial ischemia and infarction in mCRC (1.2% with Stivarga vs 0.4% with placebo). Withhold Stivarga in patients who develop new or acute cardiac ischemia or infarction, and resume only after resolution of acute cardiac ischemic events if the potential benefits outweigh the risks of further cardiac ischemia.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Reversible Posterior Leukoencephalopathy Syndrome (RPLS) occurred in 1 of 1200 Stivarga-treated patients across all clinical trials. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Confirm the diagnosis of RPLS with MRI and discontinue Stivarga in patients who develop RPLS.

Gastrointestinal Perforation or Fistula: Gastrointestinal perforation or fistula occurred in 0.6% of 1200 patients treated with Stivarga across clinical trials. In GIST, 2.1% (4/188) of Stivarga-treated patients developed gastrointestinal fistula or perforation: of these, 2 cases of gastrointestinal perforation were fatal. Permanently discontinue Stivarga in patients who develop gastrointestinal perforation or fistula.

Wound Healing Complications: Treatment with Stivarga should be stopped at least 2 weeks prior to scheduled surgery. Resuming treatment after surgery should be based on clinical judgment of adequate wound healing. Stivarga should be discontinued in patients with wound dehiscence.

Embryo-Fetal Toxicity: Stivarga can cause fetal harm when administered to a pregnant woman. Use effective contraception during treatment and up to 2 months after completion of therapy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Nursing Mothers: Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Stivarga, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Most Frequently Observed Adverse Drug Reactions in mCRC: The most frequently observed adverse drug reactions (>30%) in Stivarga-treated patients vs placebo-treated patients in mCRC, respectively, were: asthenia/fatigue (64% vs 46%), decreased appetite and food intake (47% vs 28%), HFSR/PPE (45% vs 7%), diarrhea (43% vs 17%), mucositis (33% vs 5%), weight loss (32% vs 10%), infection (31% vs 17%), hypertension (30% vs 8%), and dysphonia (30% vs 6%).

Most Frequently Observed Adverse Drug Reactions in GIST: The most frequently observed adverse drug reactions (>30%) in Stivarga-treated patients vs placebo-treated patients in GIST, respectively, were: HFSR/PPE (67% vs 15%), hypertension (59% vs 27%), asthenia/fatigue (52% vs 39%), diarrhea (47% vs 9%), mucositis (40% vs 8%), dysphonia (39% vs 9%), infection (32% vs 5%), decreased appetite and food intake (31% vs 21%), and rash (30% vs 3%).

For full prescribing information, including the Boxed Warning, visit http://labeling.bayerhealthcare.com/html/products/pi/Stivarga_PI.pdf.

About Roniciclib (BAY-1000394)
Roniciclib (BAY-1000394) is an investigational oral cyclin dependent kinase (CDK) inhibitor with potential antineoplastic activity. Roniciclib binds to and inhibits the activity of CDK1/Cyclin B, CDK2/Cyclin E, CDK4/Cyclin D1, CDK6/Cyclin D3 and CDK9/Cyclin T1, serine/threonine kinases that play key roles in the regulation of tumor cell proliferation and survival.

Roniciclib is currently in Phase II of clinical development and is being investigated in multiple tumor types, including small cell lung cancer.

Roniciclib is not approved by the U.S. Food and Drug Administration, the European Medicines Agency or any other health authority.

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.

© 2015 Bayer HealthCare Pharmaceuticals Inc.
BAYER, the Bayer Cross, Xofigo and Stivarga 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]. Wayne, NJ: Bayer HealthCare Pharmaceuticals, May 2013.

2.  STIVARGA^® (regorafenib) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, April 2015.

PP-910-US-0130

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SOURCE Bayer HealthCare Pharmaceuticals Inc.