THOUSAND OAKS, CA, USA I April 4, 2017 I Amgen (AMGN) today announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) and an application for a variation to the marketing authorization to the European Medicines Agency (EMA) for XGEVA® (denosumab). The submissions to regulatory authorities seek to expand the currently approved XGEVA indication for the prevention of skeletal-related events (SREs) in solid tumors to include patients with multiple myeloma. The applications include new data from the pivotal Phase 3 head-to-head ‘482 study, the largest international multiple myeloma trial ever conducted.
XGEVA is a fully human monoclonal antibody that binds to and neutralizes RANK ligand (RANKL) – a protein essential for the formation, function and survival of osteoclasts, which break down bone – thereby inhibiting osteoclast-mediated bone destruction. XGEVA is currently indicated for the prevention of SREs in patients with bone metastases from solid tumors based on results from three previous pivotal Phase 3 head-to-head studies. In these Phase 3 studies, XGEVA demonstrated superiority in the solid tumors studied compared to zoledronic acid. In the U.S., XGEVA has a limitation of use noting that it is not indicated for the prevention of SREs in patients with multiple myeloma.
“Bone lesions are a hallmark of multiple myeloma and often result in bone complications, which can be devastating for patients. Current treatment options for bone complications are limited to bisphosphonates, which are associated with renal toxicity. Approximately 60 percent of all multiple myeloma patients have or will develop renal impairment over the course of the disease,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “XGEVA’s unique mechanism of action may offer multiple myeloma patients a novel treatment option that is not renally cleared. We look forward to collaborating with regulatory authorities to make XGEVA available to this patient population with an important unmet medical need.”
The sBLA is based on efficacy and safety data from the pivotal Phase 3 ‘482 study, which demonstrated that XGEVA is non-inferior to zoledronic acid in delaying the time to first on-study SRE in patients with multiple myeloma (HR=0.98, 95 percent CI: 0.85, 1.14; p=0.01). The secondary endpoints of superiority in delaying time to first SRE and delaying time to first-and-subsequent SRE were not met in this study. Overall survival (OS), another secondary endpoint, was also in favor of XGEVA over zoledronic acid (HR=0.90, 95 percent CI: 0.70, 1.16; p=0.41); however, it was not statistically significant. The hazard ratio of XGEVA versus zoledronic acid for progression-free survival (PFS) was 0.82 (95 percent CI: 0.68, 0.99; descriptive p=0.036). The median PFS difference between arms was 10.7 months in favor of XGEVA. These results were presented during the late-breaking abstract session at the 16th International Myeloma Workshop.
Adverse events observed in patients treated with XGEVA were consistent with the known safety profile of XGEVA. The most common adverse events (greater than 25 percent) were diarrhea (33.5 percent XGEVA and 32.4 percent zoledronic acid) and nausea (31.5 percent XGEVA and 30.4 percent zoledronic acid).
About ‘482 Study (NCT01345019)
The ‘482 study was an international, Phase 3, randomized, double-blind, multicenter trial of XGEVA compared with zoledronic acid in the prevention of SREs in adult patients with newly diagnosed multiple myeloma and bone disease. In the study, a total of 1,718 subjects (859 on each arm) were randomized to receive either subcutaneous XGEVA 120 mg and intravenous placebo every four weeks, or intravenous zoledronic acid 4 mg (adjusted for renal function) and subcutaneous placebo every four weeks. The primary endpoint of the study was non-inferiority of XGEVA versus zoledronic acid with respect to time to first on-study SRE (pathologic fracture, radiation to bone, surgery to bone or spinal cord compression). Secondary endpoints included superiority of XGEVA versus zoledronic acid with respect to time to first on-study SRE and first-and-subsequent on-study SRE and evaluation of OS. PFS was an exploratory endpoint. The safety and tolerability of XGEVA were also compared with zoledronic acid.
About Multiple Myeloma and Bone Complications
Multiple myeloma is the second most common hematologic cancer, and it develops in plasma cells located in the bone marrow microenvironment.1,2 It is typically characterized by osteolytic bone lesions, which are part of diagnosis (CRAB criteria).3,4 Each year an estimated 114,000 new cases of multiple myeloma are diagnosed worldwide, resulting in more than 80,000 deaths per year.1
More than 90 percent of patients develop osteolytic lesions during the course of the disease.3 Current treatment options for bone complications are limited to bisphosphonates, including zoledronic acid; these are cleared by the kidneys and associated with renal toxicity, which is a common complication with myeloma patients.5 Approximately 60 percent of all multiple myeloma patients have or will develop renal impairment over the course of the disease.6 Preventing bone complications is a critical aspect of caring for patients with multiple myeloma, because these events can cause significant morbidity.7
About XGEVA® (denosumab)
XGEVA targets the RANKL pathway to prevent the formation, function and survival of osteoclasts, which break down bone. XGEVA is indicated for the prevention of SREs in patients with bone metastases from solid tumors and for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. XGEVA is also indicated in the U.S. for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma.
About Amgen’s Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
References:
- Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed April 3, 2017.
- Multiple Myeloma Research Foundation. What is Multiple Myeloma? https://www.themmrf.org/multiple-myeloma/what-is-multiple-myeloma/. Accessed April 3, 2017.
- Roodman GD. Pathogenesis of myeloma bone disease. Leukemia. 2009;23(3):435–441.
- International Myeloma Working Group. International Myeloma Working Group (IMWG) Criteria for the Diagnosis of Multiple Myeloma. http://imwg.myeloma.org/international-myeloma-working-group-imwg-criteria-for-the-diagnosis-of-multiple-myeloma/. Accessed April 3, 2017.
- Terpos E, et al. International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease. J Clin Oncol. 2013;31(18):2347-57.
- Amgen Data on File.
- Drake MT. Bone disease in multiple myeloma. Oncology (Williston Park). 2009;23(14 Suppl 5):28-32.
SOURCE: Amgen
Post Views: 34
THOUSAND OAKS, CA, USA I April 4, 2017 I Amgen (AMGN) today announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) and an application for a variation to the marketing authorization to the European Medicines Agency (EMA) for XGEVA® (denosumab). The submissions to regulatory authorities seek to expand the currently approved XGEVA indication for the prevention of skeletal-related events (SREs) in solid tumors to include patients with multiple myeloma. The applications include new data from the pivotal Phase 3 head-to-head ‘482 study, the largest international multiple myeloma trial ever conducted.
XGEVA is a fully human monoclonal antibody that binds to and neutralizes RANK ligand (RANKL) – a protein essential for the formation, function and survival of osteoclasts, which break down bone – thereby inhibiting osteoclast-mediated bone destruction. XGEVA is currently indicated for the prevention of SREs in patients with bone metastases from solid tumors based on results from three previous pivotal Phase 3 head-to-head studies. In these Phase 3 studies, XGEVA demonstrated superiority in the solid tumors studied compared to zoledronic acid. In the U.S., XGEVA has a limitation of use noting that it is not indicated for the prevention of SREs in patients with multiple myeloma.
“Bone lesions are a hallmark of multiple myeloma and often result in bone complications, which can be devastating for patients. Current treatment options for bone complications are limited to bisphosphonates, which are associated with renal toxicity. Approximately 60 percent of all multiple myeloma patients have or will develop renal impairment over the course of the disease,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “XGEVA’s unique mechanism of action may offer multiple myeloma patients a novel treatment option that is not renally cleared. We look forward to collaborating with regulatory authorities to make XGEVA available to this patient population with an important unmet medical need.”
The sBLA is based on efficacy and safety data from the pivotal Phase 3 ‘482 study, which demonstrated that XGEVA is non-inferior to zoledronic acid in delaying the time to first on-study SRE in patients with multiple myeloma (HR=0.98, 95 percent CI: 0.85, 1.14; p=0.01). The secondary endpoints of superiority in delaying time to first SRE and delaying time to first-and-subsequent SRE were not met in this study. Overall survival (OS), another secondary endpoint, was also in favor of XGEVA over zoledronic acid (HR=0.90, 95 percent CI: 0.70, 1.16; p=0.41); however, it was not statistically significant. The hazard ratio of XGEVA versus zoledronic acid for progression-free survival (PFS) was 0.82 (95 percent CI: 0.68, 0.99; descriptive p=0.036). The median PFS difference between arms was 10.7 months in favor of XGEVA. These results were presented during the late-breaking abstract session at the 16th International Myeloma Workshop.
Adverse events observed in patients treated with XGEVA were consistent with the known safety profile of XGEVA. The most common adverse events (greater than 25 percent) were diarrhea (33.5 percent XGEVA and 32.4 percent zoledronic acid) and nausea (31.5 percent XGEVA and 30.4 percent zoledronic acid).
About ‘482 Study (NCT01345019)
The ‘482 study was an international, Phase 3, randomized, double-blind, multicenter trial of XGEVA compared with zoledronic acid in the prevention of SREs in adult patients with newly diagnosed multiple myeloma and bone disease. In the study, a total of 1,718 subjects (859 on each arm) were randomized to receive either subcutaneous XGEVA 120 mg and intravenous placebo every four weeks, or intravenous zoledronic acid 4 mg (adjusted for renal function) and subcutaneous placebo every four weeks. The primary endpoint of the study was non-inferiority of XGEVA versus zoledronic acid with respect to time to first on-study SRE (pathologic fracture, radiation to bone, surgery to bone or spinal cord compression). Secondary endpoints included superiority of XGEVA versus zoledronic acid with respect to time to first on-study SRE and first-and-subsequent on-study SRE and evaluation of OS. PFS was an exploratory endpoint. The safety and tolerability of XGEVA were also compared with zoledronic acid.
About Multiple Myeloma and Bone Complications
Multiple myeloma is the second most common hematologic cancer, and it develops in plasma cells located in the bone marrow microenvironment.1,2 It is typically characterized by osteolytic bone lesions, which are part of diagnosis (CRAB criteria).3,4 Each year an estimated 114,000 new cases of multiple myeloma are diagnosed worldwide, resulting in more than 80,000 deaths per year.1
More than 90 percent of patients develop osteolytic lesions during the course of the disease.3 Current treatment options for bone complications are limited to bisphosphonates, including zoledronic acid; these are cleared by the kidneys and associated with renal toxicity, which is a common complication with myeloma patients.5 Approximately 60 percent of all multiple myeloma patients have or will develop renal impairment over the course of the disease.6 Preventing bone complications is a critical aspect of caring for patients with multiple myeloma, because these events can cause significant morbidity.7
About XGEVA® (denosumab)
XGEVA targets the RANKL pathway to prevent the formation, function and survival of osteoclasts, which break down bone. XGEVA is indicated for the prevention of SREs in patients with bone metastases from solid tumors and for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. XGEVA is also indicated in the U.S. for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma.
About Amgen’s Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
References:
- Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed April 3, 2017.
- Multiple Myeloma Research Foundation. What is Multiple Myeloma? https://www.themmrf.org/multiple-myeloma/what-is-multiple-myeloma/. Accessed April 3, 2017.
- Roodman GD. Pathogenesis of myeloma bone disease. Leukemia. 2009;23(3):435–441.
- International Myeloma Working Group. International Myeloma Working Group (IMWG) Criteria for the Diagnosis of Multiple Myeloma. http://imwg.myeloma.org/international-myeloma-working-group-imwg-criteria-for-the-diagnosis-of-multiple-myeloma/. Accessed April 3, 2017.
- Terpos E, et al. International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease. J Clin Oncol. 2013;31(18):2347-57.
- Amgen Data on File.
- Drake MT. Bone disease in multiple myeloma. Oncology (Williston Park). 2009;23(14 Suppl 5):28-32.
SOURCE: Amgen
Post Views: 34
