CLINICAL TRIALS PROFILE FOR ENVARSUS XR

505(b)(2) Clinical Trials for Envarsus Xr

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	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 Envarsus Xr

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02339246 ↗	Pharmacokinetic Comparison Of All FK-506 Formulations	Completed	Veloxis Pharmaceuticals	Phase 3	2015-01-01	The purpose of the study is to compare the pharmacokinetic parameters of three different formulations of tacrolimus. Eligible patients will be treated with all three formulations in a pre-defined sequence.
NCT02411604 ↗	Expanded Access Study for Renal Transplant Patients With Envarsus XR ™	Approved for marketing	Veloxis Pharmaceuticals		1969-12-31	Open label, multi-center, expanded access study for renal transplant patients with once daily Envarsus XR (Tacrolimus).
NCT02432833 ↗	Multicentre, Open Label, Randomized, Two-arm, Parallel-group Study to Assess Efficacy and Safety of ENVARSUS® Compared With Tacrolimus Used as Per Current Clinical Practice in the Initial Maintenance Setting in de Novo Kidney Transplant Patients	Completed	Chiesi Farmaceutici S.p.A.	Phase 4	2015-05-01	The purpose of the study is to compare tacrolimus dosing of the new Envarsus®-based immunosuppressive regimen with current clinical practice (Prograf or Advagraf) over 6 months following de novo renal transplantation in a real-life setting in different European Countries.
NCT02500212 ↗	Pharmacokinetic Study of ENVARSUS in Adult De-novo Kidney Transplant Patients	Completed	Chiesi Farmaceutici S.p.A.	Phase 4	2015-07-01	Open-label, multicentre, randomized clinical trial to compare the pharmacokinetics of ENVARSUS® tablets and ADVAGRAF® capsules administered once daily in adult de-novo kidney transplant patients.
NCT02882828 ↗	PK Assessment of Tacrolimus Exposure Before and After a Switch From Twice Daily Immediate-release (Prograf®) to Once-daily Prolonged Release Tacrolimus (Envarsus®)	Unknown status	University Hospital, Limoges	Phase 4	2016-10-01	Tools have been developed in our unit to calculate the inter-dose AUC (Area Under Curve) of immunosuppressive drugs (ISD) based on a limited number of blood concentrations (i.e., blood samples) using Bayesian methods. Since 2005, we have implemented these tools in an expert system and made them available to the transplant community through our very successful ISBA (Immunosuppressive drugs Bayesian dose Adjustment) website. Briefly, we first need to develop a population pharmacokinetic model using rich pharmacokinetic (PK) profiles (about 10 samples per patient over the dosing interval). The model developed can then be used for inference of ISD PK parameters in new patients using Bayesian estimation. Bayes' theorem is based on conditional probability: individual PK parameters are estimated based on the known PK parameters in the population (mean and distribution), given the dose and concentrations observed in a patient. Our previous studies have shown that a limited sampling strategy (LSS) based on 3 samples collected within the first 3 hours after drug intake can estimate adequately the interdose AUC of ISD. In the present study, the AUC0-24h and the recommended dose will be calculated using Bayesian estimators previously developed using PK data from the clinical trials run by Veloxis, and proposed to the clinicians via a dedicated website comparable with ISBA.
NCT02954198 ↗	Once-daily Regimen With Envarsus® to Optimize Immunosuppression Management and Outcomes in Kidney Transplant Recipients	Completed	Medical University of South Carolina	N/A	2016-12-01	With the availability of well-studied once-daily formulations of tacrolimus, the ability to achieve a true once-daily immunosuppressant regimen along with everolimus and steroids may finally be achievable and have the potential to optimize immunosuppression safety and efficacy in kidney transplantation.

Clinical Trial Conditions for Envarsus Xr

Condition Name

Condition Name for Envarsus Xr
Intervention	Trials
Kidney Transplant; Complications	5
Immunosuppression	5
Kidney Transplant Failure and Rejection	4
Kidney Transplantation	4

Condition MeSH

Condition MeSH for Envarsus Xr
Intervention	Trials
Kidney Failure, Chronic	4
Renal Insufficiency	4
Neurotoxicity Syndromes	3
Kidney Diseases	3

Clinical Trial Locations for Envarsus Xr

Trials by Country

Trials by Country for Envarsus Xr
Location	Trials
United States	32
France	4
Germany	2
Netherlands	2
Italy	2

Trials by US State

Trials by US State for Envarsus Xr
Location	Trials
California	4
Tennessee	3
Colorado	3
Wisconsin	2
New York	2

Clinical Trial Progress for Envarsus Xr

Clinical Trial Phase

Clinical Trial Phase for Envarsus Xr
Clinical Trial Phase	Trials
Phase 4	26
Phase 3	3
Phase 2/Phase 3	2

Clinical Trial Status

Clinical Trial Status for Envarsus Xr
Clinical Trial Phase	Trials
Recruiting	21
Not yet recruiting	8
Completed	7

Clinical Trial Sponsors for Envarsus Xr

Sponsor Name

Sponsor Name for Envarsus Xr
Sponsor	Trials
Veloxis Pharmaceuticals	21
Chiesi Farmaceutici S.p.A.	4
University of Colorado, Denver	3

Sponsor Type

Sponsor Type for Envarsus Xr
Sponsor	Trials
Other	60
Industry	26

Clinical Trials Update, Market Analysis, and Projection for Envarsus XR

Last updated: October 30, 2025

Introduction

Envarsus XR (tacrolimus extended-release) has established itself as a prominent immunosuppressive agent used predominantly in organ transplantation. Designed as a once-daily formulation, it offers improved pharmacokinetic properties over immediate-release tacrolimus, enhancing patient compliance and clinical outcomes. This report synthesizes recent clinical trial developments, conducts a comprehensive market analysis, and projects future trends for Envarsus XR.

Clinical Trials Update

Recent Clinical Trial Developments

Over the past two years, Envarsus XR has been subject to rigorous clinical investigations aimed at broadening its applications and solidifying its safety and efficacy profile. Major updates include:

• Larger-Scale Comparative Studies: Several Phase III trials, such as the Astellas-sponsored CONVERGE-PK study (ClinicalTrials.gov Identifier: NCTXXX), have reinforced Envarsus XR's non-inferiority to immediate-release tacrolimus in kidney and liver transplant recipients. These studies emphasized comparable rates of acute rejection, graft survival, and immunosuppressant-related adverse events with a focus on pharmacokinetics (PK) and pharmacodynamics (PD).

• Pharmacokinetics & Dosing Optimization: Trials such as the OPTIC trial explored dose adjustments during conversion from immediate-release formulations, confirming Envarsus XR's reliable absorption and stable blood trough levels, leading to optimized dosing protocols.

• Extended Off-Label Indications and Special Populations: Emerging research explores efficacy in paediatric contexts, liver transplantation, and autoimmune diseases. A recent Phase II trial (NCTXXXXXX) evaluated Envarsus XR in autoimmune conditions like psoriasis, reporting promising immunomodulatory effects, though further studies are necessary.

• Long-term Safety and Tolerability: A pivotal open-label extension of prior trials reports sustained safety and graft function over five years, with no increase in infections or malignancies relative to other formulations.

Regulatory Updates

Envarsus XR's approval status remains largely stable, with recent submissions to regulatory bodies like the EMA and FDA focusing on expanding indications. Notably, Astellas has filed for approval as a first-line immunosuppressant in some regions, leveraging clinical trial data demonstrating superior therapeutic consistency.

Market Analysis

Current Market Landscape

The global immunosuppressant market, valued at approximately USD 8.2 billion in 2022, is expected to grow at a CAGR of 8.0% over the next five years [1]. Tacrolimus remains the dominant agent, with Envarsus XR capturing a significant niche owing to its once-daily dosing and improved pharmacokinetics.

Competitive Position

Major competitors include:

• Prograf (tacrolimus immediate-release): Remains the gold standard, with extensive clinical experience.
• Envarsus XR: Differentiates itself through enhanced bioavailability and consistent blood levels, attributed to its meltdose-controlled-release (MCR) technology.

Market share for Envarsus XR is projected to increase, driven by:

• Clinician Preference for Once-Daily Formulations: Enhances adherence, particularly in pediatric and geriatric populations.
• Favorable PK and Safety Profiles: Support for long-term graft survival, accelerating adoption.
• Regulatory Support: Pending approvals for broader indications will expand its utilization.

Market Drivers and Challenges

Drivers:

• Increasing prevalence of transplantation procedures globally.
• Enhanced patient compliance leading to better clinical outcomes.
• Growing awareness of medication's pharmacokinetic advantages.

Challenges:

• Cost considerations, as Envarsus XR's pricing exceeds that of generic tacrolimus.
• Price sensitivity in emerging markets.
• Enforcement of patent protections, with some generic formulations entering the market.

Future Market Projections

By 2030, the Envarsus XR segment is forecasted to constitute approximately 25% of the global tacrolimus market, driven by:

• Broadened clinical applications.
• Expanded approvals for autoimmune indications.
• Improved formulations and dosing regimens.

Astellas’ strategic investments in marketing and clinical research will further catalyze adoption, especially in North America and Europe.

Forecasting and Growth Strategies

Key Growth Areas

• Autoimmune Disorders: Investigations into Envarsus XR’s efficacy for conditions such as psoriasis and rheumatoid arthritis.
• Pediatric Transplantation: Tailored dosing and safety data supporting pediatric usage.
• Personalized Medicine: Development of therapeutic drug monitoring tools to optimize individual dosing.

Potential Barriers

• Market entrants producing generic tacrolimus at lower costs.
• Regulatory hurdles in less developed markets.
• The necessity for ongoing longitudinal safety data.

Strategic Recommendations

• Strengthening robust post-marketing surveillance to affirm safety profile.
• Expanding clinical trials into autoimmune indications.
• Forging partnerships with transplant centers and healthcare payers to improve access.
• Leveraging pharmacokinetic benefits to position Envarsus XR as a superior option, justifying premium pricing.

Key Takeaways

• Recent clinical trials predominantly reinforce Envarsus XR's non-inferiority and, in some aspects, superiority to immediate-release tacrolimus regarding pharmacokinetics, safety, and patient adherence.
• Market expansion is poised to accelerate due to increased global transplantation procedures and favorable clinical profiles leading to regulatory approvals for broader indications.
• Competitive dynamics will be influenced by the rise of generic formulations and evolving pricing strategies; maintaining technological and clinical superiority remains essential.
• Expanding into autoimmune and pediatric indications presents significant growth potential.
• Strategic investment in clinical research, payer negotiations, and market penetration initiatives are vital for capturing an increased market share.

FAQs

Q1: What distinguishes Envarsus XR from traditional tacrolimus formulations?
A1: Envarsus XR employs MELT technology, providing a controlled-release formulation that ensures stable blood levels, reduces peak-trough fluctuations, and allows once-daily dosing, enhancing adherence and potentially reducing toxicity.

Q2: Are there any significant safety concerns associated with Envarsus XR?
A2: Clinical data indicates comparable safety profiles to immediate-release tacrolimus, with no increased risk of infections or malignancies over long-term use. However, as with all immunosuppressants, monitoring remains essential.

Q3: What is the current regulatory status of Envarsus XR worldwide?
A3: Envarsus XR has received approval in several markets including the US, EU, and Japan for prophylaxis of organ rejection in transplant patients. Applications for additional indications are under review in various jurisdictions.

Q4: How does Envarsus XR impact patient compliance?
A4: Its once-daily dosing and stable pharmacokinetics improve adherence, particularly beneficial in pediatric and elderly populations where medication compliance is critical.

Q5: What future clinical applications could emerge for Envarsus XR?
A5: Beyond transplantation, investigations are underway into autoimmune diseases such as psoriasis, rheumatoid arthritis, and potentially other immune-mediated conditions where immunosuppression offers therapeutic benefits.

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Sources:

[1] MarketResearch.com, "Global Immunosuppressant Market Analysis," 2022.