CLINICAL TRIALS PROFILE FOR PROGRAF

505(b)(2) Clinical Trials for PROGRAF

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT00717470 ↗	A Study in Kidney Transplant Subjects to Investigate the Optimal Suppression of Immunity to Help Prevent Kidney Rejection	Completed	Astellas Pharma Inc	Phase 4	2008-05-14	To compare how well the new formulation of Tacrolimus® used once daily, in combination with other drugs helps prevent the rejection of a new kidney after transplantation compared to the twice daily dose of Tacrolimus
New Formulation	NCT04489134 ↗	P-glypoprotein Inhibition Effect on the Pharmacokinetics of Two Tacrolimus Formulations: Prolonged and Extended-release	Not yet recruiting	Rennes University Hospital	Phase 2	2021-11-01	Tacrolimus is a drug administered orally available with different formulations: immediate release (Prograf®), prolonged-release (Advagraf®) and an extended-release one named LCP-Tacro (Envarsus®), formulated using the Melt-Dose process. Tacrolimus is a lipophilic macrolide drug able to passive transmembrane diffusion. Its bioavailability displays a large interindividual variability, from 9 to 43%. Indeed, tacrolimus is a substrate of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4). P-gp is an efflux protein mainly located at the apex of the epithelia of the intestine, lymphocyte, kidney and blood-brain barrier. P-gp therefore limits the intestinal resorption of tacrolimus and also its diffusion into its target compartment (i.e the lymphocyte. The expression of this protein is different throughout the digestive tract with maximum expression at the ileal level. CYP3A4 is a coenzyme that is responsible of more than 90% of the metabolism of tacrolimus, at the digestive and hepatic level. Both P-gp and CYP3A4 play a role in tacrolimus absorption/diffusion process. A new formulation of tacrolimus, LCP-Tacro, (Envarsus®) was approved in 2014. Its efficacy was compared to Prograf® in two phase III de novo or switch Prograf® trials in kidney transplantation. With tacrolimus, there is a strong inter-individual pharmacokinetic variability which, to date, has not been fully characterized. Variations in bioavailability may partly explain this high variability. The different formulations are resorbed at distinct gastrointestinal sites which could explain different absorptions between Prograf/Advagraf and LCP-Tacro forms. These findings raise the question of the role of P-gp in explaining the difference in bioavailability between formulations. The use of a P-gp inhibitor could therefore have a different impact on exposure to different galenic formulations. Verapamil is an inhibitor of P-gp and CYP 3A4, which is frequently prescribed and recommended by FDA for drug-drug interaction studies aiming at evaluating P-gp substrates, used in healthy volunteers at dosages up to 240 mg/D13-14. Otherwise, verapamil-tacrolimus interaction has been characterized in vitro. It has also been shown that inhibitory effect of verapamil at a single dose of 120 mg administered one hour prior to the administration of a P-gp substrate exhibited an optimum power of inhibition. The safety of Advagraf® and Envarsus® administrations have already been subjected to several phase I trials in healthy volunteers reinforcing the knowledge of their safety profile. The aim of the study is to compare the interaction profile of Advagraf® and Envarsus® when co-administered with verapamil in healthy subjects and to provide guidelines on tacrolimus dosage adjustment in such cases.

All Clinical Trials for PROGRAF

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00002831 ↗	Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myelogenous or Acute Leukemia	Completed	National Cancer Institute (NCI)	Phase 1/Phase 2	1995-08-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of high-dose chemotherapy plus peripheral stem cell transplantation in treating patients with chronic myelogenous or acute leukemia.
NCT00002831 ↗	Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myelogenous or Acute Leukemia	Completed	M.D. Anderson Cancer Center	Phase 1/Phase 2	1995-08-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of high-dose chemotherapy plus peripheral stem cell transplantation in treating patients with chronic myelogenous or acute leukemia.
NCT00034528 ↗	Stem Cell Transplantation After Reduced-Dose Chemotherapy for Patients With Sickle Cell Disease or Thalassemia	Terminated	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	2001-09-01	The purpose of this study is to find out if using a lower dose of chemotherapy before stem cell transplantation can cure patients of sickle cell anemia or thalassemia while causing fewer severe side effects than conventional high dose chemotherapy with transplantation.
NCT00036153 ↗	Study to Assess Efficacy of Tacrolimus + Methotrexate Versus Placebo + Methotrexate in Treatment of Rheumatoid Arthritis	Completed	Astellas Pharma US, Inc.	Phase 3	2002-03-01	The purpose of this study is to evaluate the efficacy of the combination of tacrolimus + methotrexate compared to methotrexate alone in the treatment of the signs and symptoms of rheumatoid arthritis over 6 months in patients with partial response to methotrexate.
NCT00036153 ↗	Study to Assess Efficacy of Tacrolimus + Methotrexate Versus Placebo + Methotrexate in Treatment of Rheumatoid Arthritis	Completed	Astellas Pharma Inc	Phase 3	2002-03-01	The purpose of this study is to evaluate the efficacy of the combination of tacrolimus + methotrexate compared to methotrexate alone in the treatment of the signs and symptoms of rheumatoid arthritis over 6 months in patients with partial response to methotrexate.
NCT00039377 ↗	Chemotherapy, Imatinib Mesylate, and Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia	Completed	National Cancer Institute (NCI)	Phase 2	2002-04-01	This phase II trial studies how well giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation works in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation may be an effective treatment for acute lymphoblastic leukemia.

Clinical Trial Conditions for PROGRAF

Condition Name

Condition Name for PROGRAF
Intervention	Trials
Kidney Transplantation	45
Leukemia	33
Myelodysplastic Syndrome	31
Liver Transplantation	26

Condition MeSH

Condition MeSH for PROGRAF
Intervention	Trials
Leukemia	88
Myelodysplastic Syndromes	62
Preleukemia	58
Leukemia, Myeloid, Acute	56

Clinical Trial Locations for PROGRAF

Trials by Country

Trials by Country for PROGRAF
Location	Trials
United States	861
Canada	65
China	46
France	27
Korea, Republic of	26

Trials by US State

Trials by US State for PROGRAF
Location	Trials
Texas	66
California	60
Pennsylvania	50
Ohio	47
New York	45

Clinical Trial Progress for PROGRAF

Clinical Trial Phase

Clinical Trial Phase for PROGRAF
Clinical Trial Phase	Trials
PHASE4	2
Phase 4	106
Phase 3	53

Clinical Trial Status

Clinical Trial Status for PROGRAF
Clinical Trial Phase	Trials
Completed	225
Recruiting	55
Terminated	44

Clinical Trial Sponsors for PROGRAF

Sponsor Name

Sponsor Name for PROGRAF
Sponsor	Trials
National Cancer Institute (NCI)	93
Astellas Pharma Inc	55
M.D. Anderson Cancer Center	38

Sponsor Type

Sponsor Type for PROGRAF
Sponsor	Trials
Other	375
Industry	224
NIH	117

Last updated: May 20, 2026

Prograf (tacrolimus) Clinical Trials Update, Market Analysis, and 2026–2035 Projections

Prograf is the branded form of tacrolimus, a calcineurin inhibitor used to prevent organ transplant rejection. Market activity is driven by (1) transplant procedure volumes, (2) competitive pressure from generics and authorized/biocomparable tacrolimus products, (3) safety monitoring and adherence in long-term therapy, and (4) the pace of new-to-brand reformulations and alternative tacrolimus delivery systems.

What matters for near-term performance (2026–2029): (a) erosion of branded share versus tacrolimus immediate-release and extended-release generics, (b) payer preference for lower-cost products, and (c) any label expansions or formulation-specific advantages that can be carved out as formulary differentiators.

High-level projections (directional): Tacrolimus’s category growth tracks with transplant volumes and shifts between formulations. Pricing and volume mix typically move against branded makers as patent and exclusivity headwinds progress. The key variable for Prograf is not new MOA uptake, but brand-specific defensibility through formulation, contracting, and originator switching costs.

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What is Prograf (tacrolimus) and what are the current clinical trial directions?

Featured-snippet answer: Prograf’s current clinical development focus is predominantly on tacrolimus-based optimization rather than a new mechanism, centered on comparative efficacy/tolerability, exposure targeting, and formulation convenience for long-term maintenance immunosuppression after transplant.

Which transplant settings generate most late-stage activity?

Trials most commonly target:

• Kidney transplant maintenance and conversion strategies
• De novo kidney transplant immunosuppression regimens
• Liver transplant maintenance with tacrolimus exposure management
• Switching studies among tacrolimus formulations and dosing strategies
• Adherence and pharmacokinetic (PK) exposure control at stable trough targets

What endpoints dominate tacrolimus studies?

• Biopsy-proven rejection rates
• Graft survival and patient survival
• Tacrolimus trough concentration stability within target ranges
• Renal function markers (serum creatinine, eGFR trends)
• Safety: nephrotoxicity, neurotoxicity, infection burden, metabolic effects (glucose, lipids)
• Drug-related discontinuation rates and adherence metrics

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What clinical trials are ongoing for Prograf tacrolimus in 2025–2026?

A complete, accurate “ongoing trials” list requires live registry extraction by trial ID and sponsor, which is not available in the provided context. Under the operating constraint to avoid incomplete or inaccurate listings, no registry-specific table is produced here.

What trial types are most likely to appear in recent updates?

• Conversion trials: switching from another tacrolimus brand/formulation to Prograf or vice versa, using target trough windows.
• Exposure-response and therapeutic drug monitoring (TDM) studies: refine how trough monitoring is scheduled and interpreted.
• Comparative formulation studies: immediate-release vs modified-release or once-daily dosing formats.
• Safety intensification mitigation: protocols that reduce nephrotoxicity while maintaining rejection prevention.

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How does Prograf compare with other tacrolimus products (immediate vs extended-release) in clinical practice?

Featured-snippet answer: In practice, tacrolimus products differ mainly by dosing frequency, formulation pharmacokinetics, and clinical protocols for monitoring. Efficacy is generally comparable when trough targets are maintained.

Key practical differentiators

• Dosing frequency and administration burden
• PK profile shape and trough-to-AUC relationship
• TDM operational requirements (frequency, target stability)
• Product switching protocols and “stability after conversion” evidence
• Convenience and adherence impacts in long-term maintenance

Originator vs generic switching effects

Competitive dynamics for tacrolimus brands often hinge on:

• Formulary switching policies
• Patient and center preference for stable exposure
• Clinician comfort with therapeutic monitoring under new products
• Real-world discontinuation rates after switching

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When do key Prograf exclusivity and patent protections end for tacrolimus in the US?

Featured-snippet answer: Tacrolimus is broadly available as generics in the US; the brand’s remaining protection is typically limited to specific manufacturing/formulation patents and any remaining regulatory exclusivity tied to new approvals, not core tacrolimus molecule protection.

A complete exclusivity and patent runout requires a jurisdiction-by-jurisdiction Orange Book and patent-set mapping that is not available here in sufficient detail to deliver a correct expiration timeline.

What protection categories usually still affect brand value?

• Product-specific formulation/process patents
• Granted but late-expiring patents on manufacturing impurities or crystalline forms
• Any remaining FDA exclusivity tied to specific NDA/changes (less common for mature tacrolimus brands)
• Patent terms that can influence authorized generic and “skinny label” timing

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What is the Orange Book status of Prograf and how many patents cover it?

Featured-snippet answer: Prograf’s Orange Book entry historically lists multiple patents covering drug substance and/or drug product aspects, but the exact count and the active/inactive status must be pulled from FDA’s Orange Book to be accurate.

No Orange Book patent listing is included here because the necessary complete listing is not present in the supplied context.

How does Orange Book status translate to generic entry risk?

For mature tacrolimus brands, generic entry risk is typically high, with brand differentiation shifting to:

• contracting and rebates
• therapeutic monitoring protocols
• switching behavior and retention

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What generic entry risks exist for Prograf and how do Paragraph IV challenges affect timing?

Featured-snippet answer: In tacrolimus, generic entry risk is generally established as a function of market maturity and existing generic availability. The remaining brand impact comes from formulation-specific litigation and any residual exclusivity rather than blocking broad access to tacrolimus.

A precise Paragraph IV challenge count, filers, and outcomes require direct litigation docket extraction or Orange Book challenge records that are not included in the provided information.

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What patent litigation affects Prograf and what settlements changed the market?

Featured-snippet answer: Prograf litigation is typically centered on tacrolimus formulation/process patents and FDA generic pathway approvals. Settlement-driven market shifts can occur through licensing, supply agreements, or “at-risk” launch windows.

Specific case identifiers, filing dates, and settlement terms cannot be reported accurately without access to the underlying case record and the factual docket history.

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How strong is the patent estate for Prograf tacrolimus across US, EU, and UK?

Featured-snippet answer: The overall patent strength for Prograf as a brand is usually limited versus first-in-class protection because tacrolimus is an established molecule with multiple generics. Remaining strength is generally concentrated in product-specific patents and process-related claims, where enforcement is narrow but can delay specific product variants.

A jurisdiction-by-jurisdiction patent strength score requires a complete patent list, remaining term analysis, and claim scope mapping that is not available here.

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What formulations are protected for Prograf and what are the practical barriers for generic and biosimilar-style competition?

Featured-snippet answer: For small-molecule tacrolimus, the competitive barrier is not biosimilar-style comparability but generic equivalence under ANDA (or product-specific development where relevant). Practical barriers include:

• sustaining therapeutic exposure under modified-release formulations
• demonstrating bioequivalence under switching protocols
• meeting manufacturing and impurity specifications tied to formulation patents/process claims

No definitive protected formulation list is provided without reliable claim-to-product mapping.

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How does Prograf perform in the market versus tacrolimus competitors and extended-release products?

Market structure and drivers

Tacrolimus market shares are usually segmented by:

• kidney vs liver transplant demand
• immediate-release vs extended/modified-release formats
• originator brand vs generics and authorized generics
• hospital formulary contracting patterns

Competitor landscape categories

• Generic tacrolimus immediate-release products (price and volume dominant)
• Other tacrolimus brands and modified-release formats (protocol-driven adoption)
• Authorized generics in some markets (brand-like distribution under different pricing)

Where brand pricing power can survive

• centers that enforce stable tacrolimus product continuity
• patient populations with conversion sensitivity
• contracts where the originator is used as default

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Clinical and commercial projection: what is the likely 2026–2035 trajectory for Prograf revenue?

Featured-snippet answer: Prograf revenue is projected to grow slowly or decline modestly in mature markets, with category growth offset by branded share erosion to generics, moderated by switching friction, monitoring protocols, and any retained benefits from formulation convenience.

Projection logic used for mature tacrolimus brands

• Transplant volumes: modest structural growth in many geographies, limited by incidence and healthcare capacity
• Tacrolimus price: continued downward pressure as branded share shifts to generics
• Mix: possible stability or slight improvement if modified-release adoption favors specific manufacturers
• Competition: high generic penetration reduces upside from pure volume

Directional scenario table (no numeric revenue claims without source-backed baseline)

Scenario	Branded share trajectory	Pricing trajectory	Category volume impact	Net brand revenue direction
Base	Gradual erosion	Downward	Stable	Low single-digit decline to flat
Upside	Slower switch away (contracting)	Mild stabilization	Moderate transplant growth	Flat to low growth
Downside	Faster formulary switching	Steeper price cuts	Weak growth	Mid single-digit decline

A numeric forecast requires an auditable starting revenue base, geographic split, and competitor share assumptions which are not present in the provided context.

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Regulatory and uptake considerations: how do FDA and payer dynamics influence Prograf outcomes?

FDA-related uptake drivers

• Bioequivalence standards and formulation comparability determine interchangeability in practice
• Labeling specifics for dosing, trough monitoring, and adverse event management influence clinician acceptance

Payer and HTA dynamics

• Managed care formularies typically favor least-cost tacrolimus equivalents after bioswitch style switch-back thresholds are met
• Hospital contracting and bundled procurement often reduce brand premium

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Key takeaways

• Prograf’s clinical relevance remains tied to transplant immunosuppression protocol optimization and therapeutic drug monitoring rather than a new mechanism of action.
• Market performance for Prograf is primarily a function of branded share versus generics and contractual switching frictions, not overall tacrolimus category growth alone.
• Patent and exclusivity-driven protection is typically narrow for mature tacrolimus brands; remaining value is concentrated in product-specific protections and commercial arrangements.
• 2026–2035 revenue direction is likely flat to declining modestly, with upside contingent on slower formulary erosion and any defensible formulation advantages.

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FAQs

1. What drives tacrolimus brand retention in transplant centers?
   Stable trough targets, protocolized therapeutic drug monitoring, and institutional contracting that reduces switching frequency.

2. Do extended-release tacrolimus formulations change rejection outcomes versus Prograf?
   When exposure is kept within target ranges, clinical outcomes are generally comparable, with differences more tied to PK convenience and monitoring efficiency.

3. How do generics affect therapeutic drug monitoring and safety perception for tacrolimus?
   Switching can change observed trough dynamics temporarily; centers rely on tighter monitoring during conversion windows.

4. What payer policies most influence Prograf coverage?
   Least-cost formulary rules, automatic substitution policies for equivalent tacrolimus products, and prior authorization requirements for brand use.

5. Is the main competitive threat for Prograf in the US coming from ANDAs?
   Yes, competition is primarily from ANDA generics and authorized equivalents, with remaining brand impacts driven by formulation-specific barriers and contracting.

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References (APA)

1. U.S. Food and Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA.
2. U.S. National Library of Medicine. (n.d.). ClinicalTrials.gov. NIH.