CLINICAL TRIALS PROFILE FOR PROLIA

Biosimilar Clinical Trials for PROLIA

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.
NCT04591275 ↗	Clinical Efficacy and Safety Comparative Study Between CMAB807 Injection and Prolia® .	Recruiting	Shanghai Biomabs Pharmaceutical Co., Ltd.	Phase 3	2021-03-31	evaluate the differences in effectiveness and safety between CMAB807( potential biosimilar) and Prolia(original product)
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.
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 PROLIA

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.
NCT01358669 ↗	Effect of Denosumab on Inflammatory Osteolytic Lesion Activity in Total Hip Arthroplasty	Unknown status	Amgen	Phase 2	2011-12-14	Although hip replacement surgery is a successful way of dealing with the pain and immobility caused by hip arthritis, 10% of the hip replacements carried out in the UK fail within 10 years. The main reason for this is the development periprosthetic osteolysis, that is, loss of bone around the site of the hip replacement. The osteolysis is thought to be due to the small particles of debris worn from the surfaces of the hip implant. These particles cause a reaction in the blood cells around the joint which in turn affects bone cells and leads to a loss of bone around the implant. The joint implant will then eventually become loose and unstable, a condition known as aseptic loosening. At present the only way to treat aseptic loosening is to have another operation to secure the hip joint, known as revision surgery. Revision surgery is not always successful and exposes the patient to the risk of major surgery. In this study we explore the potential for giving a medication (denosumab) that may prevent the loss of bone around the hip replacement implant. We will recruit patients who have been listed for revision surgery. One group of patients will be given a single dose of denosumab; another group will be given a placebo (dummy drug). At the time of the revision surgery a small sample of the bone from around the hip replacement will be taken and examined under the microscope. Comparisons will be made between the patients having the denosumab and those having placebo to find out whether the denosumab is having a beneficial effect on the bone surfaces. If successful, this study will lead to further studies to develop the use of denosumab to prevent aseptic loosening.
NCT01358669 ↗	Effect of Denosumab on Inflammatory Osteolytic Lesion Activity in Total Hip Arthroplasty	Unknown status	University of Sheffield	Phase 2	2011-12-14	Although hip replacement surgery is a successful way of dealing with the pain and immobility caused by hip arthritis, 10% of the hip replacements carried out in the UK fail within 10 years. The main reason for this is the development periprosthetic osteolysis, that is, loss of bone around the site of the hip replacement. The osteolysis is thought to be due to the small particles of debris worn from the surfaces of the hip implant. These particles cause a reaction in the blood cells around the joint which in turn affects bone cells and leads to a loss of bone around the implant. The joint implant will then eventually become loose and unstable, a condition known as aseptic loosening. At present the only way to treat aseptic loosening is to have another operation to secure the hip joint, known as revision surgery. Revision surgery is not always successful and exposes the patient to the risk of major surgery. In this study we explore the potential for giving a medication (denosumab) that may prevent the loss of bone around the hip replacement implant. We will recruit patients who have been listed for revision surgery. One group of patients will be given a single dose of denosumab; another group will be given a placebo (dummy drug). At the time of the revision surgery a small sample of the bone from around the hip replacement will be taken and examined under the microscope. Comparisons will be made between the patients having the denosumab and those having placebo to find out whether the denosumab is having a beneficial effect on the bone surfaces. If successful, this study will lead to further studies to develop the use of denosumab to prevent aseptic loosening.
NCT01358669 ↗	Effect of Denosumab on Inflammatory Osteolytic Lesion Activity in Total Hip Arthroplasty	Unknown status	Sheffield Teaching Hospitals NHS Foundation Trust	Phase 2	2011-12-14	Although hip replacement surgery is a successful way of dealing with the pain and immobility caused by hip arthritis, 10% of the hip replacements carried out in the UK fail within 10 years. The main reason for this is the development periprosthetic osteolysis, that is, loss of bone around the site of the hip replacement. The osteolysis is thought to be due to the small particles of debris worn from the surfaces of the hip implant. These particles cause a reaction in the blood cells around the joint which in turn affects bone cells and leads to a loss of bone around the implant. The joint implant will then eventually become loose and unstable, a condition known as aseptic loosening. At present the only way to treat aseptic loosening is to have another operation to secure the hip joint, known as revision surgery. Revision surgery is not always successful and exposes the patient to the risk of major surgery. In this study we explore the potential for giving a medication (denosumab) that may prevent the loss of bone around the hip replacement implant. We will recruit patients who have been listed for revision surgery. One group of patients will be given a single dose of denosumab; another group will be given a placebo (dummy drug). At the time of the revision surgery a small sample of the bone from around the hip replacement will be taken and examined under the microscope. Comparisons will be made between the patients having the denosumab and those having placebo to find out whether the denosumab is having a beneficial effect on the bone surfaces. If successful, this study will lead to further studies to develop the use of denosumab to prevent aseptic loosening.
NCT01377467 ↗	Denosumab for Prevention of Osteoporosis in Renal Transplant Recipients	Completed	Rudolf Wuethrich	Phase 3	2011-06-01	The primary objective of the study is to examine the effect of denosumab on lumbar spine bone mineral density (BMD) after one year of treatment in newly transplanted renal allograft recipients. Secondary endpoints include BMD changes at the total hip and the femoral neck, changes in body height, changes in bone mineral metabolism parameters, incidence of fractures, and allograft function at one year. Safety measurements include the occurrence of rejection episodes, infectious complications, graft loss and mortality. - Trial with medicinal product
NCT01465568 ↗	Denosumab in Current Users of Bisphosphonates for Glucocorticoid-induced Osteoporosis	Completed	Tuen Mun Hospital	Phase 4	2011-12-01	The purpose of this study is to study the efficacy of denosumab, a new drug, in the treatment of osteoporosis in patients using bisphosphonates.

Clinical Trial Conditions for PROLIA

Condition Name

Condition Name for PROLIA
Intervention	Trials
Osteoporosis	25
Postmenopausal Osteoporosis	10
Osteoporosis, Postmenopausal	7
Infertility, Male	4

Condition MeSH

Condition MeSH for PROLIA
Intervention	Trials
Osteoporosis	47
Osteoporosis, Postmenopausal	19
Breast Neoplasms	5
Bone Diseases, Metabolic	4

Clinical Trial Locations for PROLIA

Trials by Country

Trials by Country for PROLIA
Location	Trials
United States	42
China	27
Poland	22
Denmark	7
Hungary	7

Trials by US State

Trials by US State for PROLIA
Location	Trials
New York	12
Massachusetts	5
New Jersey	5
Texas	4
Pennsylvania	3

Clinical Trial Progress for PROLIA

Clinical Trial Phase

Clinical Trial Phase for PROLIA
Clinical Trial Phase	Trials
PHASE4	3
PHASE3	3
PHASE1	3

Clinical Trial Status

Clinical Trial Status for PROLIA
Clinical Trial Phase	Trials
Recruiting	34
Completed	30
Active, not recruiting	7

Clinical Trial Sponsors for PROLIA

Sponsor Name

Sponsor Name for PROLIA
Sponsor	Trials
Amgen	14
Massachusetts General Hospital	5
Martin Blomberg Jensen	5

Sponsor Type

Sponsor Type for PROLIA
Sponsor	Trials
Other	88
Industry	42
NIH	6

Prolia (denosumab) Clinical Trials Update, Market Analysis, and Projection

Last updated: April 26, 2026

What is Prolia and where does it fit commercially?

Prolia is denosumab (RANKL inhibitor) given by subcutaneous injection for patients with osteoporosis at high fracture risk and for several oncology-related bone disease settings. The product is widely used in postmenopausal osteoporosis, men with osteoporosis at high fracture risk, and glucocorticoid-induced osteoporosis. Outside the U.S., Prolia is also used for additional osteoporosis-related indications depending on local approvals and label language.

Core commercial identity

• Drug: denosumab
• Brand: Prolia (vs Xgeva for oncology bone disease)
• Class: RANKL antibody
• Mechanism: inhibits osteoclast-mediated bone resorption via RANKL blockade
• Regulatory basis: approvals tied to fracture endpoint programs and sustained bone turnover suppression consistent across osteoporosis populations (product label)

Key reference label endpoints (regulatory positioning)

• Prolia is indicated to reduce risk of fracture in osteoporosis populations (postmenopausal women; men with osteoporosis; glucocorticoid-induced osteoporosis in specific populations) and to increase bone mass; label dosing is subcutaneous with interval therapy (see Prolia prescribing information).
• Prolia dosing interval is every 6 months (see prescribing information).
  Source: Amgen Prolia U.S. prescribing information [1].

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What does the clinical trial pipeline look like for Prolia?

For Prolia, near-term clinical trial activity is best described as a mix of: (1) label-expansion and subpopulation trials in osteoporosis and bone health, (2) comparative effectiveness and adherence/real-world evidence programs, and (3) safety and long-term management studies related to denosumab continuation and discontinuation outcomes.

Publicly disclosed trial landscape (high level)

• Osteoporosis and fracture reduction programs: ongoing or completed studies continue to reinforce fracture risk reduction and characterize safety in osteoporotic subgroups (age, baseline fracture history, comorbidities, and glucocorticoid exposure).
• Real-world outcomes and persistence: programs quantify adherence patterns for 6-month dosing and evaluate downstream effects on fractures and bone turnover markers.
• Discontinuation and rebound risk management: trials and observational cohorts address bone loss and vertebral fracture risk after stopping denosumab and evaluate transition strategies to bisphosphonates.

How to interpret “update” for Prolia Denosumab has an established efficacy and safety profile across osteoporosis indications, so pipeline value typically concentrates in:

• expanding eligible patient populations,
• improving management protocols for discontinuation,
• refining safety monitoring frameworks,
• sustaining payer relevance through outcomes evidence.

Clinical evidence base used by regulators and payers

• Prolia’s fracture-risk reduction is supported by randomized controlled programs with clinically meaningful endpoints (e.g., new vertebral fractures and hip fracture risk reductions depending on the trial and population).
• Long-term extension data support persistent suppression of bone turnover markers and continued fracture risk reduction while patients remain on therapy (see prescribing information summary).
  Source: Amgen Prolia U.S. prescribing information [1].

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What are the most consequential safety and management points affecting trial design and market behavior?

Denosumab’s market behavior depends on patient management after discontinuation and the management of hypocalcemia risk.

Safety and management elements that drive real-world adoption and treatment planning

1. Hypocalcemia risk
   • Requires attention to baseline calcium and vitamin D status and monitoring in at-risk patients (renal impairment is a key driver).
   • Impacts eligibility criteria in studies and payer policies.
2. Rebound bone turnover after discontinuation
   • Leads to increased bone resorption markers and associated vertebral fracture risk in some patients after stopping.
   • Drives “transition therapy” protocols in both clinical care and ongoing studies.

Label-linked risk controls

• The prescribing information includes warnings about hypocalcemia and recommends monitoring and correction of calcium/vitamin D as appropriate.
• The label also includes discontinuation-related warnings and the need for careful management of therapy cessation to avoid rebound effects.
  Source: Amgen Prolia U.S. prescribing information [1].

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What is the current market structure for Prolia?

Prolia is a leading osteoporosis therapy in markets that reimburse antibody-based antiresorptives and maintain preference for agents that reduce adherence burden relative to weekly or monthly dosing.

Positioning vs other osteoporosis drug classes

• Antiresorptives: Prolia competes with oral bisphosphonates and other injectables (where available).
• Dosing advantage: 6-month subcutaneous administration supports adherence, which matters for payers focused on persistence and reduced fracture burden.
• Patient selection: high-risk categories (prior fractures, older age, intolerance or contraindication to bisphosphonates) tend to favor Prolia.

Competitive set (practical payer view)

• Oral bisphosphonates (cost-leadership in many formularies but adherence drag)
• Other injectable antiresorptives (where present)
• Anabolic therapies in select high-risk populations (depending on label access)

Why this structure matters Prolia’s commercial outcomes depend on:

• persistence (staying on schedule every 6 months),
• physician selection of high-risk patients,
• reimbursement and formulary tiering,
• management of discontinuation and transition therapy to prevent rebound events.

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How big is the Prolia opportunity and how is it expected to grow?

A precise global forecast requires current consensus market sizing and country-level reimbursement trajectories. The public domain supports directionally accurate market drivers for denosumab-class therapies, but a complete, numeric forecast for Prolia alone cannot be produced here without explicit market data sources in the provided material.

What can be stated from foundational facts

• Denosumab remains a cornerstone option for high-risk osteoporosis populations due to efficacy and dosing convenience (label-based positioning) [1].
• Market performance is sensitive to payer restrictions on initiation and continuation, and to clinical protocols governing discontinuation.

Projection logic used by industry Projections are typically modeled as:

• Eligible population growth (aging demographics, glucocorticoid use patterns)
• Treatment penetration (share of osteoporosis patients on therapy)
• Persistence-adjusted dosing (every-6-month adherence)
• Formulary dynamics (tier placement, prior authorization, step therapy)
• Safety management effects (risk management influences willingness to start/continue)

For Prolia specifically, the key “slope” variables are persistence and continuation, since a disruption can cause clinically relevant rebound effects that shift utilization patterns and payer scrutiny.

Sources: Prolia prescribing information [1].

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What are the key commercial risks and downside scenarios for Prolia?

1) Discontinuation and patient management

• If clinical practices or protocols fail to ensure transition management after stopping, rebound vertebral fracture risk can drive negative utilization decisions, more monitoring requirements, and payer restrictions.

2) Payer restriction tightening

• Formularies can narrow reimbursement if cost-effectiveness declines relative to alternatives or if comparative effectiveness evidence changes prescribing habits.

3) Safety concerns impacting start rates in at-risk groups

• Hypocalcemia risk and monitoring requirements can reduce initiation in patients with impaired calcium homeostasis unless systems are in place.

All points map directly to label warnings and monitoring guidance for Prolia.
Source: Amgen Prolia U.S. prescribing information [1].

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What does the evidence say about duration of therapy and adherence effects?

Prolia is an interval therapy and its clinical impact depends on consistent dosing.

Label-linked dosing reality

• The prescribed schedule is once every 6 months, which supports persistence compared with regimens that require more frequent administration (label dosing schedule) [1].

Adherence and persistence implications

• Higher persistence supports fracture-risk reduction consistency.
• Missed or delayed doses can undermine the risk reduction profile and can contribute to rebound-type safety concerns after long gaps.

Source: Amgen Prolia U.S. prescribing information [1].

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How should businesses frame the “clinical trials update” for decision-making?

For Prolia, the update is not about first-in-class shifts. It is about execution: what ongoing studies and evidence are likely to affect (1) label utility breadth, (2) management protocols, and (3) payer acceptance and continuation policies.

Decision-critical themes

• Confirmation of fracture-risk reduction across subgroups
• Validation and standardization of discontinuation management
• Safety monitoring refinement (hypocalcemia prevention and surveillance)
• Real-world persistence and adherence outcomes that map to dosing interval design

Sources: Prolia prescribing information [1].

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Key Takeaways

• Prolia is denosumab with a core osteoporosis franchise built on fracture-risk reduction and 6-month subcutaneous dosing, making persistence a central determinant of both clinical and commercial outcomes. [1]
• Clinical activity for Prolia centers on subpopulation evidence, real-world outcomes, and protocols addressing discontinuation management and hypocalcemia risk, which directly influence uptake and payer policies. [1]
• Market projections for Prolia are most sensitive to persistence/continuation, formulary access, and patient selection rules, since treatment interruption can create clinically meaningful rebound effects. [1]

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FAQs

1. Is Prolia the same drug as Xgeva?
   Yes, both are denosumab, but they are marketed under different brands and have different indications and dosing contexts. [1]

2. What dosing schedule is used for Prolia?
   Prolia is administered subcutaneously once every 6 months. [1]

3. What safety issue affects osteoporosis prescribing for Prolia?
   Hypocalcemia risk in at-risk patients and the need for appropriate monitoring and correction of calcium/vitamin D status. [1]

4. Why does stopping Prolia require careful management?
   Discontinuation can lead to increased bone turnover and associated vertebral fracture risk in some settings, so transition strategies and follow-up are critical. [1]

5. What evidence underpins Prolia’s osteoporosis use?
   Randomized clinical programs using fracture endpoints and long-term extension safety and efficacy data summarized in the prescribing information. [1]

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References

[1] Amgen. (n.d.). Prolia (denosumab) prescribing information. https://www.accessdata.fda.gov/ (Amgen label document).