CLINICAL TRIALS PROFILE FOR COAGULATION FACTOR IX (RECOMBINANT)

Biosimilar Clinical Trials for coagulation factor ix (recombinant)

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

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT05668650 ↗	Double-blind Study to Evaluate the PK, Efficacy, Safety and Immunogenicity of MB12 Versus Keytruda® in Stage IV NSCLC	Not yet recruiting	Syneos Health	Phase 3	2023-03-01	This is a randomized, multicenter, multinational, double-blind, and parallel-group study to evaluate the PK, efficacy, safety and immunogenicity of MB12 (proposed pembrolizumab biosimilar) versus Keytruda® in subjects with newly diagnosed stage IV non-squamous NSCLC. This study is planned to be conducted in approximately 48 sites in 7 countries, a total of 174 subjects will be enrolled. Eligible subjects will be randomized in a 1:1 ratio to receive MB12 or Keytruda® at a dose of 200 mg every 3 weeks. Subjects will be stratified by gender (male versus female) and ECOG status (0 versus 1) as both factors are considered to have the potential to influence PK properties of pembrolizumab to some extent. The study will consist of 2 periods defined as follows: - Main Study Period from Screening up to Cycle 6 included. - Extended Treatment Period from Cycle 7 up to Week 52 for those subjects who demonstrate clinical benefit from the treatment (complete response [CR], partial response [PR], and stable disease [SD]). They will continue treatment until disease progression, intolerance to the study drug, treatment discontinuation for other reason, or up to Week 52, whichever occurs first. A Data Safety Monitoring Board (DSMB) will assess the safety data periodically and will recommend to the sponsor whether to continue, modify, or stop the trial on the basis of safety considerations. After the first 10 subjects have received at least 2 cycles of treatment, the DSMB will review the accumulated safety data, and the first meeting will take place. Subsequent meetings will be performed as per the DSMB charter.
NCT05668650 ↗	Double-blind Study to Evaluate the PK, Efficacy, Safety and Immunogenicity of MB12 Versus Keytruda® in Stage IV NSCLC	Not yet recruiting	Laboratorio Elea Phoenix S.A.	Phase 3	2023-03-01	This is a randomized, multicenter, multinational, double-blind, and parallel-group study to evaluate the PK, efficacy, safety and immunogenicity of MB12 (proposed pembrolizumab biosimilar) versus Keytruda® in subjects with newly diagnosed stage IV non-squamous NSCLC. This study is planned to be conducted in approximately 48 sites in 7 countries, a total of 174 subjects will be enrolled. Eligible subjects will be randomized in a 1:1 ratio to receive MB12 or Keytruda® at a dose of 200 mg every 3 weeks. Subjects will be stratified by gender (male versus female) and ECOG status (0 versus 1) as both factors are considered to have the potential to influence PK properties of pembrolizumab to some extent. The study will consist of 2 periods defined as follows: - Main Study Period from Screening up to Cycle 6 included. - Extended Treatment Period from Cycle 7 up to Week 52 for those subjects who demonstrate clinical benefit from the treatment (complete response [CR], partial response [PR], and stable disease [SD]). They will continue treatment until disease progression, intolerance to the study drug, treatment discontinuation for other reason, or up to Week 52, whichever occurs first. A Data Safety Monitoring Board (DSMB) will assess the safety data periodically and will recommend to the sponsor whether to continue, modify, or stop the trial on the basis of safety considerations. After the first 10 subjects have received at least 2 cycles of treatment, the DSMB will review the accumulated safety data, and the first meeting will take place. Subsequent meetings will be performed as per the DSMB charter.

All Clinical Trials for coagulation factor ix (recombinant)

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000463 ↗	Post Coronary Artery Bypass Graft (CABG) Study	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1987-04-01	To determine the relative effectiveness of moderate versus more aggressive lipid lowering, and of low dose anticoagulation versus placebo, in delaying saphenous vein coronary bypass graft atherosclerosis and preventing occlusion of saphenous grafts of patients with saphenous vein coronary bypass grafts placed 1 to 11 years previously.
NCT00000529 ↗	Tamoxifen Study	Completed	National Cancer Institute (NCI)	Phase 3	1992-05-01	To assess the impact of tamoxifen on development of breast cancer, coronary heart disease, and bone fractures. The National Cancer Institute initiated the prevention trial under its National Surgical Adjuvant Breast and Bowel Project (NSABP). The National Heart, Lung, and Blood Institute provided support to obtain blood pressure and lipid measurements, and lipoprotein and selected coagulation factor measurements in a subsample.
NCT00000529 ↗	Tamoxifen Study	Completed	NSABP Foundation Inc	Phase 3	1992-05-01	To assess the impact of tamoxifen on development of breast cancer, coronary heart disease, and bone fractures. The National Cancer Institute initiated the prevention trial under its National Surgical Adjuvant Breast and Bowel Project (NSABP). The National Heart, Lung, and Blood Institute provided support to obtain blood pressure and lipid measurements, and lipoprotein and selected coagulation factor measurements in a subsample.
NCT00000534 ↗	Calcium for Pre-Eclampsia Prevention (CPEP)	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 3	1991-03-01	To evaluate the efficacy of 2 grams per day of oral calcium supplementation in reducing the combined incidence of hypertensive disorders of pregnancy: pre-eclampsia, eclampsia, and the HELLP Syndrome (hypertension, thrombocytopenia, hemolysis, and abnormal liver function). The National Institute of Child Health and Human Development (NICHD) initiated the trial in 1991, with joint funding provided by the National Heart, Lung, and Blood Institute in fiscal years 1992, 1993, and 1995.
NCT00000534 ↗	Calcium for Pre-Eclampsia Prevention (CPEP)	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1991-03-01	To evaluate the efficacy of 2 grams per day of oral calcium supplementation in reducing the combined incidence of hypertensive disorders of pregnancy: pre-eclampsia, eclampsia, and the HELLP Syndrome (hypertension, thrombocytopenia, hemolysis, and abnormal liver function). The National Institute of Child Health and Human Development (NICHD) initiated the trial in 1991, with joint funding provided by the National Heart, Lung, and Blood Institute in fiscal years 1992, 1993, and 1995.
NCT00000690 ↗	Single Dose Pharmacokinetics of Oral Dextran Sulfate (UA001) and Intravenous Dextran Sulfate in Healthy Volunteers	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1969-12-31	To evaluate how the drug dextran sulfate (DS) is absorbed by the stomach and intestines when taken by mouth. To evaluate its effect on blood coagulation. DS has been reported to have anti-HIV activity. However, it is not known how much of the drug is absorbed into the bloodstream and can be used by the body when DS is taken by mouth.
NCT00002386 ↗	Effect of Indinavir Plus Two Other Anti-HIV Drugs on Blood Clotting in HIV-Positive Males With Hemophilia	Completed	Merck Sharp & Dohme Corp.	Phase 4	1969-12-31	The purpose of this study is to see if indinavir plus two other anti-HIV drugs affect blood clotting in HIV-positive patients with hemophilia.

Clinical Trial Conditions for coagulation factor ix (recombinant)

Condition Name

Condition Name for coagulation factor ix (recombinant)
Intervention	Trials
Healthy	34
Hemophilia A	28
Atrial Fibrillation	24
COVID-19	24

Condition MeSH

Condition MeSH for coagulation factor ix (recombinant)
Intervention	Trials
Hemorrhage	95
Hemophilia A	58
COVID-19	57
Thrombosis	56

Clinical Trial Locations for coagulation factor ix (recombinant)

Trials by Country

Trials by Country for coagulation factor ix (recombinant)
Location	Trials
China	330
Canada	192
Egypt	122
United Kingdom	103
Italy	102

Trials by US State

Trials by US State for coagulation factor ix (recombinant)
Location	Trials
California	72
Pennsylvania	63
Texas	60
New York	51
Maryland	50

Clinical Trial Progress for coagulation factor ix (recombinant)

Clinical Trial Phase

Clinical Trial Phase for coagulation factor ix (recombinant)
Clinical Trial Phase	Trials
PHASE4	28
PHASE3	15
PHASE2	32

Clinical Trial Status

Clinical Trial Status for coagulation factor ix (recombinant)
Clinical Trial Phase	Trials
Completed	554
Recruiting	252
Not yet recruiting	137

Clinical Trial Sponsors for coagulation factor ix (recombinant)

Sponsor Name

Sponsor Name for coagulation factor ix (recombinant)
Sponsor	Trials
Bayer	27
Ain Shams University	24
National Cancer Institute (NCI)	22

Sponsor Type

Sponsor Type for coagulation factor ix (recombinant)
Sponsor	Trials
Other	1649
Industry	460
NIH	67

Coagulation Factor IX (Recombinant) Clinical Trials Update, Market Analysis, and Forecast (2026–2036)

Last updated: May 25, 2026

Executive summary

• Coagulation Factor IX (recombinant) is a concentrated hemophilia B market with therapy selection driven by annualized bleeding rates, inhibitor risk, dosing burden, and payer coverage.
• The near-term competitive stack is split between long-acting FIX products (where applicable by molecule class) and standard half-life recombinant FIX products, with uptake shaped by revised prophylaxis standards and real-world data on target joint management.
• Clinical development and regulatory activity in hemophilia B increasingly targets longer-acting FIX, reduced injection frequency, and perioperative bleed coverage.
• Pricing, contracting, and channel mix (hospital vs specialty pharmacy) are the main determinants of revenue trajectory; volume growth is secondary to expanded prophylaxis penetration and patient retention on therapy.

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Which recombinant FIX products define the hemophilia B market?

Recombinant coagulation factor IX therapies marketed in hemophilia B fall into two practical commercial groups:

1. recombinant FIX products with standard or extended dosing intervals (protein replacement)
2. recombinant FIX products engineered for longer exposure (extended half-life, where designed for lower dosing frequency)

Commercial levers

• Prophylaxis penetration: dosing adherence and payer support determine sustained use.
• Switch dynamics: real-world tolerability and bleed outcomes drive line changes.
• Inhibitor management: treatment history and inhibitor status affect eligibility and outcomes.
• Perioperative coverage: surgical planning increases demand spikes, but typically not enough to move annual totals alone.

Market structure (demand by indication)

• Hemophilia B prophylaxis (non-surgical).
• Hemophilia B on-demand treatment (bleeds).
• Perioperative factor coverage (elective and emergency procedures).

How do payers decide between recombinant FIX brands?

• Clinical rationale: bleeding phenotype and prophylaxis response history.
• Economic rationale: annual cost per patient treated, dose utilization, and contract rebates.
• Operational rationale: infusion center workflows, training burden, and home administration capability.

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What are the latest clinical trial updates for recombinant FIX in hemophilia B?

Recent trial direction in hemophilia B has clustered around:

• Longer-acting recombinant FIX to reduce injection frequency.
• Extended prophylaxis schedules with endpoints tied to annualized bleeding rates, joint health measures, and pharmacokinetics.
• Safety with focused tracking on inhibitors, hypersensitivity, and thrombotic signals.
• Perioperative protocols with measured factor requirements and hemostatic efficacy.

Core trial endpoints

• Annualized bleeding rate (ABR)
• Infusion-related bleeding control during prophylaxis
• Joint health scores (target joint progression)
• Pharmacokinetics and factor exposure (relevant for dosing interval design)
• Inhibitor incidence and inhibitor titers
• Safety and tolerability, including treatment-emergent adverse events

Which trial populations are prioritized?

• Previously treated patients (PTPs) with hemophilia B
• Patient subgroups with different baseline bleeding phenotypes
• Perioperative cohorts for surgical hemostasis

What endpoints regulators emphasize for market expansion?

• Comparative effectiveness through ABR reduction vs baseline or historical controls
• Non-inferiority or clinically meaningful separation vs comparator strategies
• Inhibitor risk monitoring and durability of factor effect

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When will recombinant FIX lose exclusivity, and what does that mean for market risk?

Exclusivity timing in hemophilia B depends on the specific recombinant FIX molecule, its regulatory exclusivities, and patent estate life. The market impact typically comes from:

• US patent expiry triggering biosimilar/biogeneric or generic protein competition paths (where legally feasible).
• Settlement-driven entry windows that shift launch timing beyond nominal expiry.
• Payer contract renegotiations that accelerate or delay uptake post-entry.

Typical commercial effect after exclusivity

• Faster channel switching in pharmacy-led contracting markets.
• Slower conversion in hospital-administered pathways where physician preference and protocol inertia remain strong.
• Increased use of switching protocols if outcomes remain comparable.

How does exclusivity end by geography?

• US: patent and regulatory exclusivity govern the first wave of legal entry risk.
• EU and UK: EMA/UK processes shape subsequent entry pacing; parallel pricing reforms influence adoption.

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What is the patent estate strength for recombinant FIX products in hemophilia B?

Patent estates in hemophilia B generally cover:

• molecular construction and engineering
• formulation and stability for recombinant proteins
• manufacturing methods
• therapeutic dosing regimens and prophylaxis schedules
• device-administration systems when relevant (for delivery/administration)

Estate risk factors

• Broad composition coverage that survives portfolio dilution
• Later-expiring manufacturing or formulation patents that delay copycat ability even after functional equivalence
• Litigation posture that increases cost of challenge and deters early entry

How does patent strength affect generic entry scenarios?

• High estate density increases expected litigation cost and time-to-launch.
• Settlement likelihood increases when courts or asserted claims target commercially decisive features.

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What generic or biosimilar entry risks exist for recombinant FIX?

Competition depends on the legal and regulatory pathway for protein factor products in each jurisdiction. The commercial risk is shaped by:

• feasibility of demonstrating similarity in potency, structure, and immunogenicity
• ability to match PK exposure and clinical efficacy endpoints
• payer tolerance for switching without long-term evidence

Where entry risk tends to be highest

• Products with longer-established markets and where clinical practice already supports flexible dosing intervals.
• Contracts that allow substitution or preferred formulary shifts without mandatory physician sign-off.

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What is the regulatory status and Orange Book profile for recombinant FIX products?

Orange Book listings apply to FDA-approved drugs with patent information submitted under the Hatch-Waxman framework. For recombinant proteins, some products may have their relevant patent listings in the Orange Book and others may fall outside the Hatch-Waxman structure, affecting how entry risk is legally framed.

Practical market impact

• Orange Book “expiration + listed patents” determine the formal landscape for generic challengers in the US.
• For proteins not aligned with classic generic pathways, the relevant competitive risk shifts toward biosimilar/biogeneric-like frameworks in practice.

What milestones matter for new entrants?

• US approval and label updates (prophylaxis, dosing interval, age groups)
• Post-marketing commitments and real-world evidence programs tied to adoption
• Any REMS or safety monitoring requirements that add operational cost

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How do clinical trial outcomes translate into market share gains?

In hemophilia B, market share tends to follow a repeatable pattern:

1. Outcome credibility: low ABR in representative prophylaxis cohorts.
2. Convenience: reduced infusion frequency with stable factor levels.
3. Safety track record: low immunogenicity burden and predictable tolerability.
4. Payer alignment: contracts that convert efficacy into predictable budgets.

What metrics predict uptake acceleration?

• PK-guided dosing that reduces dose wastage
• Consistency of ABR reduction across subgroups
• Low discontinuation due to AEs or management burden
• Positive perioperative outcomes supporting elective surgery coverage

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Market projections: what growth drivers and headwinds shape revenue through 2036?

Primary growth drivers

• Increased prophylaxis adoption and retention in eligible patients
• Product lifecycle expansion via label expansions (age, dosing interval, perioperative use)
• Real-world evidence that supports payer acceptance of higher upfront pricing

Primary headwinds

• High total cost of therapy for payers and budget caps in specialty drug plans
• Contracting pressure as multiple brands compete for limited hemophilia B patient pools
• Switch-back risk if outcomes under substitute regimens underperform

Projection framework (high-level)

Revenue trajectory in hemophilia B depends on:

• patient treated base expansion (limited by prevalence)
• penetration rate of prophylaxis vs on-demand
• average selling price (ASP) and net revenue after rebates
• treatment persistence (time-on-therapy)
• product mix shift toward longer-acting options

Market outcome expectation

• Most growth comes from mix shift (standard to longer-acting where offered) and penetration/retention gains rather than steep incidence-driven demand expansion.

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Comparing recombinant FIX products: what differentiates them commercially?

Key comparative dimensions

• Dosing frequency profile
• Pharmacokinetic parameters aligned with label dosing intervals
• Immunogenicity and inhibitor risk profile
• Route and administration burden
• Evidence strength for target joint outcomes and perioperative bleed control

Competitive positioning map (commercial)

• First-line prophylaxis positioning: best-in-class convenience and ABR reduction
• Switch positioning: stable outcomes with lower burden and favorable payer contract terms
• Perioperative positioning: predictable hemostasis and operational ease

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What patent litigation and Paragraph IV-type challenges affect the recombinant FIX market?

Protein factor markets typically see litigation driven by:

• validity and infringement disputes over formulation, manufacturing, and engineered molecular features
• settlement-driven entry timing that delays competitive pressure even after practical commercial readiness

Observed litigation impact pattern

• Entry is often delayed from theoretical expiry due to injunction risk, appeal timelines, or settlement terms.
• Even when entry occurs, uptake may be slower due to evidence-generation and formulary barriers.

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What hospital and payer adoption dynamics shift forecast outcomes?

Hospital adoption

• infusion workflow integration, nursing training, and stock management
• standard-of-care protocols that determine switching frequency

Payer adoption

• prior authorization burden and outcomes-based criteria
• contract restrictions (e.g., step therapy, no-switch clauses)
• budget predictability requirements and patient capitation models

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Key takeaways

• Coagulation factor IX (recombinant) market outcomes hinge on prophylaxis penetration, dosing burden, and contracting rather than pure patient prevalence.
• Clinical development priorities are centered on longer-acting exposure, maintained bleeding control, and robust safety and inhibitor monitoring.
• Exclusivity and patent estate strength dictate timing of competitive pressure; litigation and settlements can materially shift launch schedules.
• Revenue forecasts should be modeled around mix shift, persistence, and net price after rebates, with competition slowing the growth rate once multiple options reach formulary parity.

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FAQs

1. How do annualized bleeding rate and pharmacokinetic matching affect coverage decisions for recombinant FIX?
2. What clinical endpoints matter most for perioperative indications of hemophilia B recombinant FIX products?
3. How do inhibitor history and immunogenicity profiles influence eligibility and switch decisions among recombinant FIX therapies?
4. What are the main drivers of treatment persistence (adherence) in prophylaxis dosing schedules for recombinant FIX?
5. How does contract design (rebates, step therapy, no-switch clauses) change projected market share after competitor entry?

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References (APA)

1. FDA. (n.d.). Drugs@FDA: Drug Approval Reports and Labels. U.S. Food and Drug Administration.
2. FDA. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration.
3. EMA. (n.d.). European Public Assessment Reports (EPAR) for medicinal products. European Medicines Agency.
4. World Federation of Hemophilia. (n.d.). Hemophilia Treatment Guidelines. World Federation of Hemophilia.