Amgen Statement on the Economic Benefit of XGEVA® (denosumab) Versus Zoledronic Acid in the Prevention of Bone Complications in Multiple Myeloma

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 as well as renal impairment, which are both part of diagnosis (CRAB criteria).^3,4 About 90 percent of patients develop osteolytic lesions during the course of the disease, which can increase the risk of bone complications, also known as skeletal-related events (which are pathologic fracture, radiation to bone, surgery to bone or spinal cord compression).³ 

Preventing bone complications is a critical aspect of caring for multiple myeloma patients with bone metastases, because these events can cause significant morbidity.⁵ Skeletal-related events in real-world multiple myeloma patients drive up healthcare costs by approximately 75 percent.⁶ The average annual increase in multiple myeloma healthcare costs due to skeletal-related events is about $80,000.⁶ To date, current treatment options to prevent bone complications in patients with multiple myeloma are limited to bisphosphonates, including zoledronic acid, which are cleared through the kidneys.⁷ XGEVA is currently under investigation to prevent skeletal-related events in multiple myeloma patients. 

On October 26, results from the XGEVA Global Economic Model (X-GEM) were presented during an oral session at the Lymphoma & Myeloma 2017 Congress in New York. The analysis demonstrated a net monetary benefit of $10,259 per patient in favor of XGEVA^® (denosumab) compared to zoledronic acid in the prevention of skeletal-related events in newly diagnosed multiple myeloma patients.*

The X-GEM utilized results from the Phase 3 ‘482 study**, as well as real-world data, to determine the outcomes and costs of newly diagnosed multiple myeloma patients at risk of experiencing skeletal-related events. The Model considered a lifetime horizon, with 50 percent of patients alive at 6.5 years, to capture outcomes occurring from bone lesion diagnosis to death.

In the analysis, cost comprised direct and indirect costs, including drug acquisition, drug administration, adverse event costs, skeletal-related event management costs, short-term disability and productivity loss costs and myeloma treatment costs. The Model considered outcomes including the following: skeletal-related event rates, adverse events, overall survival and progression-free survival, the latter being a key driver of the resulting net monetary benefit. Progression-free survival was a pre-specified exploratory endpoint, while not powered to determine statistical significance, it showed patients treated with XGEVA experienced a 10.7-month longer median duration of progression-free survival versus those on zoledronic acid (46.1 months versus 35.4 months, respectively). 

The X-GEM is based on an internationally recognized and validated incremental cost-effectiveness ratio methodology to assess the value of a medical intervention. The X-GEM also demonstrated that XGEVA was cost-effective compared to zoledronic acid applying a willingness-to-pay threshold of $150,000 per quality-adjusted life-year (QALY), irrespective of which zoledronic acid price was selected (average sales price or wholesale acquisition cost).

XGEVA was found to be non-inferior to zoledronic acid in preventing skeletal-related events in the largest Phase 3 international study in multiple myeloma patients. The thorough approach taken in the X-GEM not only considers costs but the overall value that XGEVA provides to myeloma patients over the course of their disease. If approved by regulatory agencies, XGEVA may save money for society in comparison to zoledronic acid and should be considered an important new treatment option for the prevention of skeletal-related events in multiple myeloma patients.

XGEVA is currently indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors and is the number one prescribed bone targeting agent by oncologists for this indication in the U.S. XGEVA is currently not indicated for the prevention of skeletal-related events in patients with multiple myeloma.

In April 2017, Amgen announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for XGEVA. The submission seeks to expand the currently approved XGEVA indication to include patients with multiple myeloma. In June 2017, the FDA accepted the sBLA and set a Prescription Drug User Fee Act (PDUFA) action date of Feb. 3, 2018.

*Net monetary benefit was calculated by applying a willingness to pay of $150,000 per QALY, multiplied by the incremental health benefits (QALYs), minus the incremental costs, and is expressed in the common metric of dollars.

**Data from the Phase 3 ‘482 study was presented at the 16^th International Myeloma Workshop (IMW) in New Delhi: Link

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