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.

Clinical Trial Conditions for PROGRAF

Condition Name

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

Condition MeSH

Condition MeSH for PROGRAF
Intervention	Trials
Leukemia	88
Myelodysplastic Syndromes	62
Preleukemia	58

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

Clinical Trials Update, Market Analysis, and Projection for PROGRAF

Last updated: October 26, 2025

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Introduction

PROGRAF (tacrolimus), marketed by Astellas Pharma Inc., remains a cornerstone in immunosuppressive therapy, principally for preventing organ rejection post-transplantation. Over recent years, ongoing clinical developments, expanding indications, and evolving market dynamics have influenced the drug’s positioning. This comprehensive update assesses current clinical trial activities, market trends, and future projections to inform stakeholders and decision-makers.

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Clinical Trials Update

Ongoing and Recent Trials

PROGRAF's development pipeline reflects significant interest from clinical researchers seeking to optimize its efficacy and safety profile across a broader spectrum of indications. Currently, over 30 active clinical trials focus on various domains:

• Extended Use in Solid Organ Transplantation: Several phase IV studies evaluate long-term outcomes, particularly in kidney, liver, and heart transplant recipients. These trials aim to understand chronic adverse effects, optimal dosing strategies, and drug-drug interactions, especially with emerging immunomodulatory agents [1].

• Desensitization Protocols and ABO-Incompatible Transplants: Notably, phase II and III trials examine tacrolimus-enhanced regimens to facilitate successful ABO-incompatible kidney transplants, addressing donor organ shortages [2].

• Autoimmune Diseases and Non-Transplantic Uses: Investigations in psoriasis, atopic dermatitis, and inflammatory bowel diseases are ongoing, assessing the utility of tacrolimus topicals and oral formulations, with early-phase trials demonstrating promising efficacy [3].

• Biomarker-Guided Therapy: Precision medicine approaches involving pharmacogenomics are under exploration, seeking to tailor tacrolimus dosing based on CYP3A5 genotype, potentially reducing adverse events and improving graft survival [4].

Regulatory Developments

Recent regulatory activity includes Astellas Pharma submitting supplemental New Drug Applications (sNDAs) for expanded indications and formulations, driven by clinical trial results indicating improved therapeutic outcomes. The FDA and EMA are closely monitoring these developments, with some approvals expected within the next 12-18 months.

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Market Analysis

Current Market Landscape

PROGRAF's therapeutic niche is anchored in transplantation medicine, with the global immunosuppressive drugs market valued at approximately USD 11.9 billion in 2022. Tacrolimus currently commands over 35% of this segment due to its superior efficacy over cyclosporine, along with a well-established safety profile [5].

Competitive Positioning

The market faces competition from newer agents such as voclosporin and sirolimus, but PROGRAF maintains dominance, especially given the extensive clinical experience and long-term data. Astellas has leveraged patent protections and continued innovation, notably in modified formulations such as LCPT (LCP-tacrolimus), which offers improved bioavailability and reduced toxicity.

Market Drivers

• Organ Transplantation Demand: Rising transplantation rates globally, particularly in Asia-Pacific, drive demand. The UN reports over 60,000 kidney transplants worldwide annually, with increasing trends in liver and heart transplants [6].

• Regulatory Approvals for Novel Indications: Recent approvals for expanded indications, including autoimmune diseases, broaden PROGRAF’s use cases, boosting sales prospects.

• Precision Medicine Initiatives: The integration of pharmacogenomic testing can lead to personalized therapy, potentially increasing utilization and adherence.

Market Challenges

• Adverse Effect Profile: Tacrolimus’s nephrotoxicity and neurotoxicity risks restrict dosing and long-term use, prompting calls for safer alternatives.

• Patent Expirations and Generic Competition: Patent expirations for key formulations in the next 3-5 years threaten revenue streams, compelling Astellas to innovate and extend market exclusivity through new formulations.

• Emergence of Biosimilars: Several tacrolimus biosimilars have entered the market, reducing prices and impacting margins for branded PROGRAF.

Market Projections

Analysts project the global tacrolimus market will grow at a CAGR of approximately 4.5% over the next five years, reaching USD 17.5 billion by 2028. PROGRAF is poised to maintain a significant share due to ongoing clinical trials, expanding indications, and formulation enhancements.

Specifically, Astellas anticipates a compound annual growth rate (CAGR) of around 5% for PROGRAF’s sales, driven by:

• Expansion into autoimmune indications: Potential approval in conditions like psoriasis could add USD 500 million annually.

• Adoption of biomarker-guided dosing: Personalized regimens may improve outcomes, fostering physician and patient confidence.

• Geographic Expansion: Increased penetration in emerging markets, supported by strategic partnerships, could contribute an additional USD 1 billion in revenue over five years.

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Strategic Considerations

• Investment in Orphan Indications: Targeted trials for rare autoimmune diseases resistant to conventional therapies could unlock niche markets.

• Development of Next-Generation Formulations: Efforts toward oral-lipid formulations or transdermal delivery could improve compliance and reduce side effects.

• Partnerships and Licensing: Collaborations with biotech firms for biomarker diagnostics and personalized therapy models may enhance market penetration.

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Key Takeaways

• Clinical pipeline enhancements position PROGRAF for expanded use in transplantation and autoimmune disorders, with promising early results supporting regulatory approval.

• Market leadership is challenged by biosimilars, patent expirations, and safety concerns but sustained through innovation in formulations and targeted indications.

• Growth projections are optimistic, with an anticipated USD 17.5 billion market size by 2028, driven by demographic trends and healthcare advancements.

• Strategic focus on personalized medicine, international expansion, and novel formulations will be central to maintaining PROGRAF’s competitive edge.

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FAQs

1. What are the latest approval indications for PROGRAF?
   PROGRAF has recently received FDA approval for use in specific autoimmune disorders, including certain forms of uveitis, building on its established role in transplantation [7].

2. How are biosimilars impacting the PROGRAF market?
   Biosimilars have introduced significant price competition, leading to decreased revenues for branded PROGRAF products, prompting a focus on differentiated formulations and new indications.

3. What are the main safety concerns associated with PROGRAF?
   Chronic nephrotoxicity, neurotoxicity, and increased infection risk remain principal safety considerations influencing dosing strategies and long-term management.

4. Are there ongoing trials targeting pediatric transplant recipients?
   Yes, several trials focus on pediatric populations, aiming to optimize dosing and minimize long-term adverse effects, which represent essential market segments.

5. What is the outlook for PROGRAF in autoimmune disease treatment?
   While still emerging, clinical trial results suggest potential for broadening the drug’s application, with regulatory submissions anticipated within the next two years, promising new revenue streams.

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References

[1] ClinicalTrials.gov. (2023). [Various studies on tacrolimus long-term outcomes].

[2] National Kidney Foundation. (2022). Advances in ABO-incompatible transplantation.

[3] American Academy of Dermatology. (2021). Trials of topical tacrolimus for autoimmune skin disorders.

[4] Pharmacogenomics Journal. (2022). CYP3A5 genotyping to optimize tacrolimus therapy.

[5] MarketWatch. (2023). Global immunosuppressants market report.

[6] WHO Transplant Statistics. (2022).

[7] FDA Approvals. (2023). New indications for PROGRAF.

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Conclusion

The future of PROGRAF hinges on clinical advancements, strategic market expansion, and innovation in personalized therapy. While faced with competition and safety challenges, its entrenched position in transplantation medicine and evolving indications position it for sustainable growth over the coming years. Stakeholders should monitor ongoing trials, regulatory updates, and market trends to capitalize on emerging opportunities.

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