Amgen Presents New Data From Phase 3 XGEVA® (denosumab) Study In Multiple Myeloma Patients At The 16th International Myeloma Workshop

Results to be Presented as Late-Breaking Oral Presentation
Largest International Trial Conducted in Multiple Myeloma
Study Met Primary Endpoint of Non-Inferiority Versus Zoledronic Acid in Delaying Bone Complications Known as Skeletal-Related Events

THOUSAND OAKS, CA, USA I March 3, 2017 I Amgen (NASDAQ:AMGN) today announced positive data from the Phase 3 '482 study, the largest international multiple myeloma trial ever conducted. In this study, XGEVA® (denosumab) met the primary endpoint, demonstrating non-inferiority to zoledronic acid in delaying the time to first on-study skeletal-related event (SRE) in patients with multiple myeloma (HR=0.98, 95 percent CI: 0.85, 1.14; p=0.01). The median time to first on-study SRE was similar between XGEVA (22.83 months) and zoledronic acid (23.98 months). These data will be presented today during the late-breaking abstract session at the 16th International Myeloma Workshop (IMW) in New Delhi. 

"Bone complications are devastating for patients with multiple myeloma. Renal function is a constant consideration in the treatment of multiple myeloma patients, often preventing the use of bisphosphonates, the only approved class of agents for prevention of bone complications, underscoring the need for new treatment options," said Noopur Raje, M.D., director, Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston. "The results of this study showed that denosumab may be an effective novel option that is not cleared through the kidneys that may help prevent bone complications in patients with multiple myeloma."

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. There was a suggested trend in overall survival (OS) 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.

"XGEVA is currently approved for the prevention of bone complications in patients with solid tumors based on superior clinical benefits over zoledronic acid in this setting," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The results being presented today reinforce that XGEVA's unique mechanism of action and subcutaneous administration may also offer patients with multiple myeloma a valuable alternative to the current standard of care. Amgen plans to submit these results to regulatory agencies worldwide to support a potential update to the XGEVA label."

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).

Multiple myeloma is the second most common hematologic cancer, and it develops in plasma cells located in the bone marrow microenvironment.1,2 Bone lesions appear in the vast majority of patients with multiple myeloma and weaken the bone.3 Myeloma cells induce RANK ligand (RANKL) expression, a protein essential for the formation, function and survival of osteoclasts, which break down bone.  In addition, direct RANKL expression by myeloma cells may enhance osteoclast activity in the bone microenvironment.4 Excessive RANKL can increase the risk of bone complications, including pathologic fractures, radiation therapy or surgery to the bone, and spinal cord compression.5,6

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 bone complications in patients with newly diagnosed multiple myeloma. In the study, a total of 1,718 patients (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 (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 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 characterized by a recurring pattern of remission and relapse, with patients eventually becoming refractory to treatment.7 Each year an estimated 114,000 new cases of multiple myeloma are diagnosed worldwide, resulting in more than 80,000 deaths per year.1

Bone lesions are a hallmark of multiple myeloma and often result in bone complications.3,6 Additionally, renal impairment is a common complication of multiple myeloma.8 Approximately 60 percent of all multiple myeloma patients have or will have renal impairment over the course of the disease.8 Current treatment options including zoledronic acid are cleared by the kidneys and associated with renal toxicity.6 Preventing bone complications is a critical aspect of caring for patients with multiple myeloma, because these events can cause significant morbidity.9  

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 United States (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.


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