PROLIA (denosumab)
Prolia (denosumab) is a RANK ligand inhibitor used to treat osteoporosis and increase bone mass in patients at high risk for fracture. It is indicated for postmenopausal women and men with osteoporosis, as well as individuals with glucocorticoid-induced osteoporosis. The drug is also used to address bone loss in patients receiving specific treatments for nonmetastatic prostate cancer or breast cancer. High-risk patients are defined as those with a history of osteoporotic fracture, multiple risk factors, or those who have failed or are intolerant to other therapies.
How PROLIA Works
Prolia binds to RANKL, a protein essential for the formation, function, and survival of osteoclasts, which are the cells responsible for bone resorption. By preventing RANKL from activating its receptor on the surface of osteoclasts and their precursors, the drug inhibits the breakdown of bone. This reduction in bone resorption leads to increased bone mass and strength in both cortical and trabecular bone.
Development Insights
Details
- Status
- Prescription
- First Approved
- 2010-06-01
- Patent Cliff
- 2025
- Revenue
- $1.1B (Q4-2025)
- Routes
- SUBCUTANEOUS
- Dosage Forms
- INJECTABLE
PROLIA Approval History
What PROLIA Treats
4 indicationsPROLIA is approved for 4 conditions since its original approval in 2010. These indications span multiple therapeutic areas including oncology, immunology, and more.
- Osteoporosis
- Glucocorticoid-Induced Osteoporosis
- Prostate Cancer
- Breast Cancer
PROLIA Boxed Warning
SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m 2 ), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following Prolia administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported [see Warnings and Precautions (5.1) ] . The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk ...
WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m 2 ), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following Prolia administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported [see Warnings and Precautions (5.1) ] . The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia in these patients [see Warnings and Precautions (5.1) ] . Prior to initiating Prolia in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Prolia in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ]. WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE See full prescribing information for complete boxed warning. Patients with advanced chronic kidney disease are at greater risk of severe hypocalcemia following Prolia administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported. ( 5.1 ) The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia. ( 5.1 ) Prior to initiating Prolia in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Prolia in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD. ( 2.2 , 5.1 )
PROLIA Biosimilars
10 FDA-approved10 can be substituted at the pharmacy without calling the prescriber.
What are biosimilars? Lower-cost alternatives to PROLIA with no clinically meaningful differences.
Auto-substitute OK = FDA "interchangeable" designation — pharmacist can switch without calling the doctor.
PROLIA Competitive Set
ProThree rings of competition based on shared molecular targets and treated indications.
Direct competitors
Same target(s) AND same indication — head-to-head.
MoA expansion candidates
Same target(s), different indications — where else is this mechanism being explored?
Indication competitors
Same indication, different mechanism — what else might this patient receive?
Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.
What's emerging in PROLIA's indications
See all emerging drugs →Phase 3 candidates targeting molecules with no FDA-approved drug, in indications PROLIA treats. First-in-class if their pivotal trials read out positive.
Drugs Similar to PROLIA
3 of 20FDA-approved drugs for similar conditions. Compare mechanisms and indications to understand treatment alternatives.
Clinical Trial Registry
115 trials| Trial | Sponsor ID | Phase | Status | Title |
|---|---|---|---|---|
| NCT06472050 | CIRB-2024-224-3 | Ph 4 | completed | Romosozumab Versus Denosumab in Glucocorticoid-induced Osteoporosis: an Extended Observation of a Randomized Controlled Trial at 48 Months |
| NCT03921060 | STU 052018-007 | Ph 4 | recruiting | Markers of Osteoporosis in Cystic Fibrosis |
| NCT06374459 | 202406065 BC200714 | Ph 1, Ph 2 | recruiting | Zunsemetinib in Combination With Capecitabine in Patients With Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer With Bone Metastasis |
| NCT04232657 Chronic Romo | B3415-R BAU-19-66, 1600530 | Ph 2 | active not recruiting | Romosozumab to Improve Bone Mineral Density and Architecture in Chronic SCI |
| NCT07537972 | BONE-HCC-010 | Ph 2 | not yet recruiting | Denosumab Strategy for Liver Cancer With Bone Metastases |
| NCT05010590 | 2021P002125 | Ph 4 | active not recruiting | Anabolic Therapy in Postmenopausal Osteoporosis |
| NCT03401060 DenosuMast | P150918J 2016-000596-25 | Ph 3 | completed | Interest of Denosumab Treatment in Osteoporosis Associated to Systemic Mastocytosis |
| NCT04067726 TRIDENT | 201907039 | Ph 2 | active not recruiting | RANKL Inhibition and Mammographic Breast Density |
| NCT03620019 results posted | LCCC1620 | Ph 2 | completed | Denosumab + PD-1 in Subjects With Stage III/ IV Melanoma |
| NCT06332014 | 20210123 | Ph 4 | active not recruiting | Evaluation of Efficacy and Safety of Prolia in Subjects of Male Osteoporosis in Mainland China |
| NCT05405725 results posted | ALK22/ENZ215-DEN2 2021-004811-26 | Ph 3 | completed | A Phase 3 Study to Compare Biosimilar Denosumab With Prolia® |
| NCT03839459 results posted | UMMY18121 | Ph 2 | completed | Denosumab for Smoldering Multiple Myeloma |
| NCT05419050 | 10000780 000780-D | Ph 2 | completed | Study of Denosumab for Prevention of Skeletal Disease Progression in Children With Fibrous Dysplasia |
| NCT05666310 MITO | STUDY22080139 P30AG024827 | Ph 4 | active not recruiting | Muscle Impact of Treating Osteoporosis |
| NCT06300229 NAPO | 2023-508325-27-00 | Ph 1, Ph 2 | completed | NAPO - Novel Approach for Oligospermia |
| NCT07283887 | 202509047MINA | Ph 4 | recruiting | Romosozumab and Denosumab, Alone or Combined, in Postmenopausal Osteoporosis |
| NCT07271771 DENMUSIN | CTIS: 2024-510637-18-00 CTIS: 2024-510637-18-00 | Ph 4 | recruiting | The Effect of Denosumab on Muscle and Strength and Insulin Sensitivity |
| NCT05884372 ESCORT | ELD-IIS00X | Ph 4 | completed | Efficacy and Safety of Combination Denosumab With Eldecalcitol for Postmenopausal Women With Osteoporosis.(ESCORT) |
| NCT04087096 results posted | 20187525 20187525 | Ph 4 | completed | Denosumab to Prevent High-Turnover Bone Loss After Bariatric Surgery |
| NCT05101018 | BAU-19-60 | Ph 4 | active not recruiting | Treatment With Romosozumab Versus Denosumab to Improve Bone Mineral Density and Architecture in Subacute SCI |
| NCT06524960 | 23797 JDRF Award:3-SRA-2023-1421-M-B | Ph 1, Ph 2 | recruiting | Denosumab for Type 1 Diabetes |
| NCT05493761 OsteoNAFLD | 88235 | Ph 4 | active not recruiting | Effect of Anti-osteoporotic Medications on Nonalcoholic Fatty Liver Disease |
| NCT05395091 ALVOBOND results posted | AVT03-GL-C01 | Ph 3 | completed | Multicenter Study in Postmenopausal Women With Osteoporosis, ALVOBOND |
| NCT05876949 results posted | AVT03-GL-P03 | Ph 1 | completed | AVT03 With Xgeva in Healthy Male Subjects |
| NCT04907539 results posted | RXC004/0002 | Ph 2 | completed | A Study to Assess Efficacy of RXC004 +/- Nivolumab in Ring Finger Protein 43 (RNF43) or R-spondin (RSPO) Aberrated, Metastatic, Microsatellite Stable, Colorectal Cancer After Progression on Standard of Care (SOC) |
| NCT04711109 BRCA-P | A211801 NCI-2020-11358, UG1CA189823 | Ph 3 | active not recruiting | Studying the Effect of Denosumab on Preventing Breast Cancer in Women With a BRCA1 Germline Mutation |
| NCT04907851 KEYNOTE-E86 results posted | RXC004/0003 MK-3475-E86, KEYNOTE-E86 | Ph 2 | completed | A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2) |
| NCT06749886 | 2024LY0208 | Ph 2 | recruiting | An Exploratory Study of Tislelizumab in Combination with Chemotherapy in Immuno-experienced Patients with EGFR/ALK/ROS1-negative Advanced NSCLC in the Second-line Setting |
| NCT05212337 | 19642021 | Ph 2 | active not recruiting | FITMI - First In Treating Male Infertility |
| NCT06361355 | CMAB807-I-002 | Ph 1 | completed | Study of CMAB807 Post-change in Manufacturing Site and Prolia in Healthy Volunteers |
| NCT06643780 | 2022.555 | Ph 4 | recruiting | RANK-ligand Inhibition to Combat Sarcopenia with Underlying Osteoporosis |
| NCT02771860 results posted | AGO/2015/008 2015-003223-53 | Ph 2 | completed | RANKL-blockade for the Treatment of Erosive Osteoarthritis (OA) of Interphalangeal Finger Joints |
| NCT02129699 SPLENDOUR results posted | ETOP 5-12 / EORTC 08111 2013-003156-21, 20080166 | Ph 3 | terminated | Survival imProvement in Lung cancEr iNduced by DenOsUmab theRapy |
| NCT02753283 PROUD results posted | STUDY19050268 1R01AG052123-01 | Ph 4 | completed | Preventing Osteoporosis Using Denosumab |
| NCT01575834 FRAME results posted | 20070337 2011-001456-11 | Ph 3 | completed | Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis |
| NCT02613416 Dmab results posted | 706513 | Ph 2 | completed | Denosumab and MRI Breast Imaging |
| NCT03164928 results posted | 20140444 2016-003083-39 | Ph 3 | completed | Safety and Efficiency of Denosumab in Pediatric Subjects With Glucocorticoid-induced Osteoporosis |
| NCT05126784 | AVT03-GL-P01 | Ph 1 | completed | AVT03 With Prolia in Healthy Male Subjects |
| NCT03301857 results posted | 20140114 2017-001758-32 | Ph 4 | completed | Long-term Safety Follow-up of Subjects With Giant Cell Tumor of Bone Treated With Denosumab in Study 20062004 |
| NCT03868033 DST | 201811067MIPC | Ph 4 | completed | Denosumab Sequential Therapy |
| NCT06314698 | IIT-2024-0011 | Ph 3 | not yet recruiting | Narlumosbart Compared With Denosumab in Patients With Multiple Myeloma Bone Disease |
| NCT03925532 results posted | I 78618 NCI-2019-01921, I 78618 | Ph 2 | completed | Denosumab in Treating Patients With Bone Loss Due to Donor Stem Cell Transplant |
| NCT02470091 results posted | AOST1321 NCI-2015-00543, s15-01360 | Ph 2 | completed | Denosumab in Treating Patients With Recurrent or Refractory Osteosarcoma |
| NCT02792413 HDENO | RECHMPL15_0496 UF 9676 | Ph 4 | terminated | Study Evaluating Denosumab on Bone and Vascular Metabolism in Osteoporotic Chronic Kidney Disease |
| NCT04026256 results posted | 2018P002537 5R01AR073191-04 | Ph 4 | completed | Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration |
| NCT03030196 | 01112016 2016-003546-84 | Ph 2 | completed | Denosumab and Male Infertility: a RCT |
| NCT03623633 | 2018P001612 | Ph 4 | active not recruiting | Comparative Antiresorptive Efficacy Discontinuation of Denosumab |
| NCT05813665 | JMT103-011 | Ph 3 | not yet recruiting | A Study to Evaluate the Efficacy and Safety of Narlumosbart (JMT103) in Patients With Giant Cell Tumor of Bone |
| NCT02352753 OI results posted | 20130173 2014-000184-40 | Ph 3 | terminated | Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI |
| NCT03638128 results posted | 20170534 2018-000550-21 | Ph 3 | terminated | Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta |
Showing 50 of 115 trials
Active Pipeline
Ongoing clinical trials by development phase
Key Completed Trials
Completed studies with published results, ranked by significance
Trial Timeline
Full development history with FDA approval milestones
Understanding FDA Approval Types
| Count | Type | What it means |
|---|---|---|
| - | ORIG | Original approval - drug first enters market |
| - | SUPPL - Efficacy | New indication (new disease/condition approved) |
| - | SUPPL - Labeling | Label text changes (warnings, dosing updates) |
| - | SUPPL - Manufacturing | Production changes (new facility) |
| - | SUPPL - Chemistry | Formulation changes (new dosage strength) |
Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.
PROLIA FDA Label Details
Indications & Usage
FDA Label (PDF)PROLIA is indicated for the treatment of Osteoporosis; Glucocorticoid-Induced Osteoporosis; Prostate Cancer; Breast Cancer.
WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m 2 ), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following Prolia administration. Severe hypocalcemia resulting in hospit...
Pro Intelligence Preview
Deep insights for PROLIA
Revenue Insights
- • Q4-2025: $1.1B
- • Historical trend analysis
Patent Timeline
- • Cliff: 2025
- • Generic/biosimilar risk
Trial Analysis
- • 15 total trials
- • Stage: Stable
Competitive Landscape
- • 20 similar drugs
- • Same target/indication analysis
Full approval history • All patents • Revenue trends • Competitor analysis
Data Sources
Data sourced from official FDA and NIH databases. Click links to verify on original sources.
How We Calculate These Metrics
Trial Activity Stage
Measures the current development activity pattern based on trial phases, status, and trends. Important: This measures R&D activity, not commercial lifecycle.
Trial statuses: "Active" means recruiting or ongoing. "Completed" means reached planned endpoint. "Terminated" means stopped early—often due to safety, efficacy, or business reasons.
- Growth: High proportion of early-phase trials (Phase 1/2), active development
- Expansion: Significant Phase 3 activity, approaching or pursuing approvals
- Mature: Substantial Phase 4 post-marketing studies
- Stable: Mixed phase distribution, steady development
- Declining: Low active trial ratio, reduced R&D investment