Denosumab products (Prolia, Xgeva) and the listed biosimilars are RANKL (receptor activator of nuclear factor kappa‑B ligand) inhibitors. FDA‑labeled indications include treatment of postmenopausal osteoporosis, increasing bone mass in men with osteoporosis, glucocorticoid‑induced osteoporosis, fracture prevention in patients receiving ADT for nonmetastatic prostate cancer and in women receiving adjuvant aromatase inhibitor therapy for breast cancer, prevention of skeletal‑related events in multiple myeloma and bone metastases, treatment of giant cell tumor of bone, and treatment of hypercalcemia of malignancy refractory to bisphosphonates.
The policy aligns coverage with FDA indications and guideline‑based definitions of fracture risk (for example, AACE/ACE and WHO T‑score definitions are used). For osteoporosis and many other indications the policy requires prior trial and failure of bisphosphonate therapy (generic alendronate preferred) at maximally indicated doses unless one of the documented bypass conditions applies (for example, contraindication to all bisphosphonates, clinically significant adverse effects to both oral and IV bisphosphonates, loss of BMD or lack of BMD increase after ≥12 months of bisphosphonate therapy, or an osteoporotic/fragility fracture while on bisphosphonate therapy).
Per updated prescribing information and policy revisions, boxed warnings note that CKD‑MBD markedly increases the risk of severe hypocalcemia and that patients with advanced chronic kidney disease are at greater risk; the policy advises evaluation for CKD‑MBD prior to initiating Prolia (and certain biosimilars) and supervision by a provider experienced in CKD‑MBD where applicable.
The policy also incorporates guideline and regulatory considerations for oncology settings (including state‑level prohibitions on step therapy for certain metastatic cancer scenarios) when applying prior‑therapy requirements.