CLINICAL TRIALS PROFILE FOR DENOSUMAB

Biosimilar Clinical Trials for denosumab

This table shows clinical trials for biosimilars. See the next table for all clinical trials

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03293108 ↗	Comparing Efficacy and Safety of AryoGen Pharmed Biosimilar Denosumab 60 mg (Arylia) Versus Prolia® in Improvement of Bone Mineral Densitometry (BMD) Among Osteoporotic Postmenopausal Women	Active, not recruiting	AryoGen Pharmed Co.	Phase 3	2017-04-29	The purpose of this study is to compare the efficacy and safety of Denosumab 60 mg produced by AryoGen Pharmed and Amgen Denosumab 60 mg among osteoporotic postmenopausal women. Postmenopausal women diagnosed with osteoporosis according to their Bone mineral density result (BMD), aged between 45 to 75 are included in this trial. This is a Phase III, randomized, two armed, double-blind, parallel, active-controlled,non-inferiority clinical trial. The eligible patients are randomized in a 1:1 ratio to receive Arylia or Prolia® subcutaneous injections, at the beginning of the trial and every 6 months at month 6 and 12, in an 18-month study period. Along with, all women will receive daily supplements containing at least 1000 mg of elemental calcium (divided into two doses) and at least 400 IU vitamin D daily during 18 months of the study. The primary objective of this study is to assess non-inferiority of test- Denosumab 60 mg (Arylia) to the reference Denosumab 60 mg (Prolia®) in terms of efficacy among osteoporotic postmenopausal women. The secondary objectives of this study are: To further compare efficacy of test- Denosumab 60 mg to reference Denosumab 60 mg; To assess the safety of test- Denosumab 60 mg compared to reference Denosumab 60 mg.
NCT04664959 ↗	A Study to Compare SB16 (Proposed Denosumab Biosimilar) to Prolia® in Postmenopausal Women With Osteoporosis	Active, not recruiting	Samsung Bioepis Co., Ltd.	Phase 3	2020-11-26	This is a randomised, double-blind, multicentre study to evaluate the efficacy, safety, PK, PD, and immunogenicity of SB16 compared to Prolia® in postmenopausal women with osteoporosis.
NCT04934072 ↗	A Study to Evaluate the Efficacy, Pharmacodynamics, Safety, and Immunogenicity of FKS518 in Postmenopausal Women With Osteoporosis	Recruiting	Fresenius Kabi SwissBioSim GmbH	Phase 3	2021-07-05	The primary objective of this study is to demonstrate equivalent efficacy of FKS518 to US-licensed Prolia in women with postmenopausal osteoporosis (PMO). Participants will be randomized at the beginning of the Double-blind Core Treatment Period (Baseline to Week 52) to receive either FKS518 or US-licensed Prolia on Day 1, and then every 26 weeks for up to 52 weeks. At the beginning of the Double-blind Transition Period (Week 52 to Week 78), participants who received US-licensed Prolia will be re-randomized to either continue receiving US-licensed Prolia every 26 weeks for up to 78 weeks, or switch to receive FKS518 every 26 weeks for up to 78 weeks. Participants who were randomized to receive FKS518 at the beginning of the Double-blind Core Treatment Period will continue to receive this treatment during the Double-blind Transition Period. For Marketing Authorization Application (MAA) in the EU and European Economic Area (EEA) only: The primary objective is to demonstrate equivalent efficacy and pharmacodynamics of the proposed biosimilar denosumab FKS518 to US-Prolia in women with PMO.
NCT05299073 ↗	A Study Comparing the Pharmacokinetic Similarity of MB09 and EU/US-Sourced Xgeva	Recruiting	mAbxience S.A	Phase 1	2022-03-01	Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare the PK, PD, safety and immunogenicity profile of MB09 with EU/US-Xgeva® in healthy male subjects. During the course of the study, the similarity in pharmacokinetics will be assessed by sampling the levels of drug in the blood, and by comparing these levels among the different administration arms. Pharmacodynamics, safety, tolerability, and immunologic response to the administered drugs will also be evaluated throughout.
NCT05338086 ↗	A Study to Compare Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of MB09 [Proposed Denosumab Biosimilar] to Prolia® [EU-sourced] in Postmenopausal Osteoporosis (SIMBA Study)	Recruiting	mAbxience S.A	Phase 3	2022-03-31	This is a randomized, double-blind, parallel, multicenter, multinational study to compare the efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of MB09 versus Prolia® in postmenopausal women with osteoporosis
NCT05419427 ↗	Denosumab Biosimilar Injection in Post Menopausal Women With Osteoporosis	Recruiting	Intas Pharmaceutical Limited	Phase 3	2021-11-11	Denosumab of Intas is biosimilar denosumab candidate under development by Intas Pharmaceutical Limited (Biopharma Division). Denosumab of Intas is already approved by Indian drug licensing authority- Drug Controller General (India) for marketing in Indian population since 2018.As per regulatory requirement, a comparative clinical study to establish Pharmacokinetic, Pharmacodynamic and Immunogenicity equivalence is required to conclude therapeutic equivalence to obtain marketing authorization of a biosimilar investigational product. This is a multicenter, randomized, double-blind, active controlled study in approximately 552postmenopausal women with osteoporosis. An extension of the study is planned after completion of the initial 1 year of treatment. This extension is with the objective of submitting data on safety, and Immunogenicity, after switching of Prolia treatment arm to either Prolia or Intas denosumab for 6 months. This switching data is applicable only for FDA submission. Only patients who have undergone PK assessment will be eligible for the extension phase.

All Clinical Trials for denosumab

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00043186 ↗	Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density	Completed	Amgen	Phase 2	2002-05-01	To determine the effect of denosumab treatment compared with placebo over 12 months on bone mineral density (BMD) of the lumbar spine in postmenopausal women with low BMD. The clinical hypothesis is that denosumab subcutaneous injections administered every 3 or 6 months for 12 months will significantly increase lumbar spine bone mineral density and will be well tolerated.
NCT00089791 ↗	A Study to Evaluate Denosumab in the Treatment of Postmenopausal Osteoporosis	Completed	Amgen	Phase 3	2004-08-01	This study will evaluate the effectiveness and safety of denosumab in treating women with Postmenopausal Osteoporosis.
NCT00091832 ↗	Denosumab (AMG 162) in Bisphosphonate Naive Metastatic Breast Cancer	Completed	Amgen	Phase 2	2004-09-01	This study is to evaluate various doses and schedules for denosumab administration and characterize the safety profile in this indication.
NCT00095498 ↗	Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis	Completed	Amgen	Phase 2	2004-08-11	This study will determine the efficacy, safety, and tolerability of denosumab (AMG 162) in the treatment of Rheumatoid Arthritis (RA).
NCT00259740 ↗	Open-Label, Phase 2, Proof of Concept Study in Multiple Myeloma - Denosumab	Completed	Amgen	Phase 2	2005-11-01	The purpose of this study is to determine if denosumab is effective in the treatment of relapsed or plateau-phase multiple myeloma.
NCT00293813 ↗	A Multicenter, Randomized Placebo Controlled Pilot MicroCT Study to Estimate the Effect of Treatment With Denosumab (AMG 162) and Alendronate Sodium in Postmenopausal Women With Low Bone Mineral Density	Completed	Amgen	Phase 2	2006-05-01	This study is structured to estimate the effect of denosumab, compared to placebo and alendronate, on several bone parameters.

Clinical Trial Conditions for denosumab

Condition Name

Condition Name for denosumab
Intervention	Trials
Osteoporosis	60
Postmenopausal Osteoporosis	21
Breast Cancer	12
Osteoporosis, Postmenopausal	10

Condition MeSH

Condition MeSH for denosumab
Intervention	Trials
Osteoporosis	103
Osteoporosis, Postmenopausal	36
Neoplasm Metastasis	20
Breast Neoplasms	20

Clinical Trial Locations for denosumab

Trials by Country

Trials by Country for denosumab
Location	Trials
United States	301
Japan	71
Canada	60
Spain	43
Australia	42

Trials by US State

Trials by US State for denosumab
Location	Trials
New York	26
California	24
Texas	16
Massachusetts	15
Pennsylvania	14

Clinical Trial Progress for denosumab

Clinical Trial Phase

Clinical Trial Phase for denosumab
Clinical Trial Phase	Trials
PHASE4	10
PHASE3	2
PHASE2	2

Clinical Trial Status

Clinical Trial Status for denosumab
Clinical Trial Phase	Trials
Completed	90
RECRUITING	72
Active, not recruiting	22

Clinical Trial Sponsors for denosumab

Sponsor Name

Sponsor Name for denosumab
Sponsor	Trials
Amgen	77
Massachusetts General Hospital	9
Shenzhen People's Hospital	7

Sponsor Type

Sponsor Type for denosumab
Sponsor	Trials
Other	227
Industry	135
NIH	11

Last updated: May 17, 2026

Denosumab clinical trials update, market analysis, and exclusivity-driven projection for 2026-2032

Denosumab (human RANKL monoclonal antibody; Prolia for osteoporosis, Xgeva for oncology bone disease) is in late-stage commercial maturity in several indications and remains exposed to biosimilar and “me-too” biologic competition risk in the US and EU. Patent and data exclusivity timelines differ by indication and geography, shaping expected pricing, volume substitution, and payer access dynamics. Market projection for 2026-2032 depends on (1) label expansion pace in oncology and metastatic bone disease, (2) biosimilar entry timing, and (3) continued safety and adherence economics versus alternative sequences (zoledronic acid and other antiresorptives).

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What clinical trials are updating denosumab in 2025 and 2026 (Prolia vs Xgeva)?

Which denosumab programs are most material to next-year label and uptake

Denosumab’s clinical trial footprint is dominated by oncology bone endpoints (skeletal-related event reduction, bone turnover markers), osteoporosis fracture prevention (vertebral, hip, nonvertebral fractures), and adjuvant/combination strategies that affect duration and sequencing.

Key categories that typically drive regulatory and commercial updates:

• Metastatic solid tumors with bone involvement: endpoints based on time to first skeletal-related event and durability of response.
• Non-metastatic indications: fracture prevention and risk stratification updates, often with subgroup analyses for adherence, renal impairment, and prior antiresorptive exposure.
• Safety and switching studies: treatment interruption, rechallenge, and transition from or to other agents to manage rebound hypercalcemia risk after discontinuation in some settings.
• Combination regimens: denosumab with systemic oncology regimens to assess additive benefit in bone outcomes without undermining tolerability.

What to watch in readouts that move markets

• Skeletal-related event efficacy consistency: any signal that supports reduced injection frequency or broader populations without added toxicity.
• Renal safety and dosing convenience: denosumab does not require renal dose adjustment, which supports uptake in CKD populations relative to bisphosphonates.
• Adherence-linked outcomes: real-world and extension trial designs that support persistence in chronic osteoporosis dosing.
• Tolerability in long duration: osteonecrosis of the jaw (ONJ) and atypical femur fracture (AFF) remain payer and clinician gating risks, so updates that refine risk mitigation can translate into formulary confidence.

Data note: a precise “2025-2026 trials update” listing requires live trial registry data and current publications for each NCT/WO number; without those inputs, an exact trial-by-trial chronology cannot be produced here.

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How strong is the denosumab patent estate, and when do key exclusivities expire?

Why exclusivity is not one date for denosumab

Denosumab’s protection is layered across:

• active ingredient biologic-related IP (composition, epitope/antibody variants, manufacturing)
• method-of-use claims (indication-specific)
• formulation and administration patents (where applicable)
• regulatory data exclusivity and pediatric exclusivity (which vary by FDA approval date and label)

Because Prolia and Xgeva are different labeled drugs even though the active is the same, expiration timing differs by indication.

Practical impact for market projections

• Biosimilar timing drives near-term pricing pressure at the national level.
• Indication-specific exclusivity can delay penetration for osteoporosis versus oncology, or vice versa.
• Litigation can extend effective exclusivity through stay mechanisms or injunctions depending on filing and settlement terms.

Data note: exact patent numbers, expiration dates, and listed Orange Book/Bioligics License Application (BLA) regulatory protections for denosumab by indication cannot be enumerated without a current, citation-backed legal dossier.

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What patents protect denosumab (Prolia and Xgeva) against biosimilar entry?

Common claim buckets that appear in denosumab patent estates

Denosumab estates typically include:

• Antibody engineering and variants: binding affinity, epitope region, and amino acid substitutions that preserve function.
• Manufacturing and purification: cell line, process steps, chromatography conditions, viral inactivation validation.
• Formulation and stabilization: buffer, excipients, pH range, surfactant content.
• Method of use: dosing regimens (interval), patient populations (high-risk osteoporosis), and oncology bone disease indications.
• Administration and monitoring: guidance around supplementation (calcium/vitamin D) or risk management.

How this affects challengers

A biosimilar candidate typically seeks to design around:

• method-of-use dosing claims and patient selection
• any formulation claims not covered by broad “same as reference” formulation permissibility
• manufacturing process claims if they can be differentiated in their process disclosures

Data note: a complete, accurate count of “how many patents” and which “numbers” protect each indication requires up-to-date regulatory and patent registry extraction.

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What is the Orange Book status of denosumab, and how does FDA listing differ for Prolia vs Xgeva?

Orange Book reality for biologics

Denosumab is a biologic approved under BLAs; biologics do not appear in the FDA’s Orange Book listing the same way as small molecules. FDA maintains biologic licensing and reference product information in different systems, while generic small molecules use the Orange Book.

For high-fidelity analysis, the relevant documents are:

• FDA BLA approval history and labeling
• biosimilar product designations and approval packages
• any publicly available FDA listing for biologics (not the classic Orange Book generics table)

Data note: without a live lookup, an “Orange Book status” mapping cannot be stated with required specificity for legal and regulatory action.

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Which companies are challenging denosumab with biosimilars or Paragraph IV-equivalents?

Entry pathway controls

For biologics, the “Paragraph IV” framing maps differently than for generics. A challenger typically files a biosimilar application under the Biologics Price Competition and Innovation Act (BPCIA), asserting similarity and seeking licensure.

Commercial implication

• If a biosimilar is approved and launched, it compresses net price through payer contracting and channel discounts.
• If litigation delays launch, the price environment stays firmer and volume growth remains tied to utilization and persistence.

Data note: a named list of challengers, filing dates, and litigation posture must be backed by current sources; this cannot be produced accurately from the information provided.

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What denosumab litigation affects market timing and generic/biosimilar launch risk?

Typical litigation timeline drivers

Denosumab’s competition risk is driven by:

• disputes over biosimilar exclusivity timing
• “resolutions” that split market access through limited launches or settlement covenants
• injunctions (rare in biosimilars compared with generics, but outcomes can still materially affect effective entry dates)

Market impact of settlements

Settlements can:

• delay the first commercial shipment
• limit indications at launch (e.g., osteoporosis first, oncology later)
• trade off indemnity and supply commitments

Data note: a case-by-case litigation table requires up-to-date docket extraction.

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How does denosumab compare with bisphosphonates on safety, adherence, and payer economics?

Clinical differentiators that shape reimbursement

Common decision drivers versus zoledronic acid and oral bisphosphonates:

• renal safety and convenience: denosumab avoids renal dose adjustment constraints
• dosing adherence: fixed interval injections can outperform oral persistence
• oncology bone convenience: oncology workflows often prefer dosing aligned with systemic therapy cycles

Cost and risk framing

Payors typically calibrate coverage based on:

• absolute fracture or skeletal-related event reduction
• ONJ/AFF risk management protocols
• documented prior therapy failure or intolerance thresholds

Commercial translation

• Denosumab outperforms where injection persistence is high and renal co-morbidity is common.
• Bisphosphonates regain share when biosimilar entry drives denosumab net price down and/or when payers shift to preferred agents with lower monitoring burden.

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Market analysis: current revenue pool, segmentation, and drivers for denosumab through 2032

Where demand is concentrated

Denosumab demand is split across:

• Prolia: osteoporosis and fracture prevention in high-risk populations (including postmenopausal osteoporosis and certain men’s osteoporosis labels depending on country)
• Xgeva: prevention of skeletal-related events in oncology settings with bone metastases and other bone involvement categories

Demand drivers that matter for 2026-2032

• Incidence and treatment penetration: aging populations and oncology treatment intensity.
• Persistence: denosumab requires ongoing dosing; persistence determines sustained revenue more than switching.
• Oncology regimen mix: growth in cancers treated with bone-targeting strategies.
• Guideline evolution: updates that either expand eligibility or tighten initial use.
• Biosimilar competitive entry: reduces net price and triggers channel migration.

Competitive landscape and pricing pressure

• Biosimilars (where approved) are the dominant pricing disruptor.
• Alternatives: denosumab competes with bisphosphonates, including intravenous and oral agents, with different safety and adherence profiles.
• Managed care: step edits and prior authorization are expected to intensify as price competition increases.

Data note: a quantified market size, CAGR, and revenue forecast requires current market data (company reports, payer claims, IQVIA/Evaluate summaries) that are not present here.

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Denosumab 2026-2032 projection: what scenarios should drive planning models?

Scenario framework

Three scenario bands typically guide biologic mature-market forecasting:

1. Base case: limited biosimilar penetration, ongoing growth in treated population, stable net price with moderate discounting.
2. Downside case: earlier-than-expected biosimilar entry or more aggressive tender contracting that compresses net price sharply.
3. Upside case: sustained label expansion and improved persistence plus slower competitive substitution.

What inputs determine which scenario dominates

• biosimilar approval dates and effective launch dates by geography
• litigation outcomes affecting first shipments
• payer contracting velocity and formulary switching rates
• denosumab persistence rates (especially after discontinuation risk management)
• safety communications and guideline adherence

Data note: without exact entry timing, patent expiration dates, and trial/readout catalysts, only a generic scenario framework can be stated; numeric projections cannot be produced with the required precision.

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Does denosumab face biosimilar substitution risk in osteoporosis versus oncology first?

Why oncology and osteoporosis may desynchronize

• oncology demand can be more concentrated in integrated oncology centers with established clinical pathways
• osteoporosis demand is broader across primary care and specialty clinics, where payer policies can move faster once price spreads are meaningful
• label exclusivity and method-of-use coverage can create indication-specific barriers

Commercial expectation

• If biosimilar launch targets one indication first, net price and volume shifts often spread over subsequent contracting cycles.
• Oncology share can be more sticky short-term due to regimen inertia, but long-term payer pressure tends to migrate preferred agents.

Data note: the sequence depends on actual launch designations and remaining indication-specific protection, which cannot be enumerated here without a live legal/regulatory dataset.

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Key Takeaways

• Denosumab’s commercial trajectory through 2032 is primarily driven by ongoing persistence and payer contracting, with biosimilar entry as the main swing factor.
• Protection and exclusivity are indication-specific for Prolia versus Xgeva, so effective competition timing can differ across osteoporosis and oncology bone disease.
• Clinical trial updates that refine risk mitigation (ONJ/AFF), support broader eligibility, or improve adherence economics are the most likely to change uptake.
• Accurate 2026-2032 numeric market projections require a current, citation-backed dataset for trial readouts, patent/exclusivity expirations, and biosimilar launch timelines.

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FAQs

1. What are denosumab’s main commercial risk factors for 2026-2032?
2. How do ONJ and AFF risk management policies affect denosumab formulary access?
3. When do biosimilar approvals typically translate into real-world prescription share loss for denosumab?
4. Do denosumab patent protections differ materially by dosing regimen (every-4-weeks vs label interval) across jurisdictions?
5. How does denosumab persistence after initiation influence long-term revenue more than patient incidence?

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References

(0 sources cited)