Envarsus (LCP-Tacro) / Asahi Kasei - LARVOL DELTA

DIFFERENTIAL IMPACT OF TACROLIMUS CONCENTRATION-TO-DOSE RATIO (C0/D RATIO) WITH DIFFERENT TACROLIMUS FORMULATIONS ON KIDNEY FUNCTION IN KIDNEY TRANSPLANT RECIPIENTS (KTRS) (ISN-WCN 2026) - "No significant differences were found between Envarsus and Advagraf after adjustment. Ongoing data collection aims to validate the C0/D ratio as a practical tool for individualized immunosuppression management."

Clinical • Infectious Disease • Solid Organ Transplantation • Transplantation

Impact of Envarsus XR® on Kidney Biopsy Subclinical Rejection and Blood Immunologic Profile (clinicaltrials.gov) - P2/3 | N=78 | Recruiting | Sponsor: Roberto Gedaly | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease

Neuro-KTR: Neurocognitive Function Changes With Extended-Release Tacrolimus Among Older Kidney Transplant Recipients (clinicaltrials.gov) - P4 | N=92 | Recruiting | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Transplantation

De-escalated Cyclophosphamide (PTCy) and Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis (clinicaltrials.gov) - P2 | N=56 | Active, not recruiting | Sponsor: Medical College of Wisconsin | Suspended ➔ Active, not recruiting

Enrollment closed • Graft versus Host Disease • Hodgkin Lymphoma • Immunology • Myelodysplastic Syndrome • HLA-B • HLA-C • HLA-DRB1

CMV Nephritis and Necrotizing Esophagoduodenitis in a D+/R– Kidney Transplant Recipient (NKF-SCM 2026) - "He completed 6 months of Valcyte prophylaxis and was maintained on Envarsus, azathioprine, and prednisone. High clinical suspicion, early tissue diagnosis, and prompt antiviral therapy are essential in managing severe CMV disease in high-risk kidney transplant recipients. Rapid initiation of ganciclovir in this case led to recovery and preserved allograft function."

Clinical • Cardiovascular • Chronic Kidney Disease • Cytomegalovirus Infection • Diabetes • Gastrointestinal Disorder • Gout • Heart Failure • Hematological Disorders • Infectious Disease • Inflammation • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Renal Calculi • Transplantation

Envarsus Versus Advagraf in De Novo Kidney Transplant Recipients: A Comparative Pharmacokinetic Study. (PubMed, Life (Basel)) - "In de novo kidney transplant recipients, Envarsus provides higher early tacrolimus exposure and consistently higher dose-normalized trough exposure than Advagraf, enabling lower maintenance doses while maintaining similar short-term effectiveness and safety. However, early overexposure was more frequent with Envarsus at 0.15 mg/kg/day, supporting careful early monitoring and consideration of lower starting doses."

Journal • PK/PD data • Transplantation

Assessment of the Intestinal CYP3A Contribution to Drug Interactions with Extended-Release Tacrolimus (LCPT) Using Grapefruit Juice. (PubMed, Clin Pharmacol Drug Dev) - "The extended-release tacrolimus formulation Envarsus (LCPT) exhibits prolonged absorption throughout the entire GI tract...Participants were administered either GFJ or water during each pharmacokinetic visit, with midazolam used as a positive control...GFJ exhibited a clinically meaningful interaction with LCPT. However, the magnitude appears less than those reported with immediate-release formulations, suggesting the extended absorption profile of LCPT may affect susceptibility to drug interactions in the intestine."

Clinical • Journal • Gastrointestinal Disorder • Transplantation

RENGEVITY-201: VEL-101 to Prevent Rejection After Kidney Transplantation (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Veloxis Pharmaceuticals

New P2 trial • Transplantation

SIMPLE: Envarsus XR Compared to Immediate Release Tacrolimus (clinicaltrials.gov) - P4 | N=261 | Completed | Sponsor: Mayo Clinic | Active, not recruiting ➔ Completed

Trial completion • Transplantation

Neuro-KTR: Neurocognitive Function Changes With Extended-Release Tacrolimus Among Older Kidney Transplant Recipients (clinicaltrials.gov) - P4 | N=92 | Not yet recruiting | Sponsor: Massachusetts General Hospital | Initiation date: May 2025 ➔ Dec 2025

Trial initiation date • Transplantation

The Highest Tacrolimus Level Ever Recorded (KIDNEY WEEK 2025) - "She was maintained on Envarsus 14mg daily, cellcept 1000mg BID, and prednisone 5mg daily...She was given 200mg IV phenytoin in successively increasing intervals to act as a cyp3A4 inducer...Discussion This case demonstrates several learning points: 1) Highlights the importance of drug-drug interactions, especially between Paxlovid and tacrolimus. 2) demonstrates the ability to use cyp3A4 inducers in a therapeutic role for tacrolimus nephrotoxicity. 3) Hints that there may be less neurotoxicity with envarsus compared to immediate-release tacrolimus."

Cardiovascular • Chronic Kidney Disease • CNS Disorders • Diabetic Nephropathy • Epilepsy • Fatigue • Hypertension • Immunology • Movement Disorders • Nephrology • Novel Coronavirus Disease • Renal Disease • Transplant Rejection

Tacrolimus-Induced Thrombotic Microangiopathy Presenting Two Years After Live-Donor Kidney Transplant (KIDNEY WEEK 2025) - "Although aHUS was in the differential diagnosis, eculizumab was not initiated due to improving allograft function after switching from Envarsus to sirolimus. One year later, she had sCr of 1.5 mg/dL while on prednisone, sirolimus, and mycophenolate...(A) Glomerulus with capillary thrombus. (PAS, 400x) (B) Blood vessel with red blood cell entrapped in vessel wall (H&E, 600x)"

Anemia • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Complement-mediated Rare Disorders • Hematological Disorders • Polycystic Kidney Disease • Thrombosis • Transplantation • HP

Comparison of Immediate- and Extended-Release Tacrolimus Formulations in Living-Donor Kidney Transplantation (LDKT) (KIDNEY WEEK 2025) - "Funding Commercial Support – Veloxis Pharmaceutical, Inc Background Standard maintenance immunosuppression in LDKT typically includes tacrolimus, mycophenolate mofetil (MMF), and ±steroids. In IPW-adjusted Cox models, compared to the Prograf reference group, there were no statistically significant differences in ACGF risk (Generic Tacrolimus: HR=1.13, 95% CI: 0.97–1.33, p =0.12; Envarsus XR: HR=0.98, 95% CI: 0.73–1.30, p =0.88) or in DCGF risk (Generic Tacrolimus: HR=1.09, 95% CI: 0.84–1.42, p = 0.51; Envarsus XR: HR=0.85, 95% CI: 0.55–1.33, p =0.48). Conclusion Envarsus XR demonstrates non-inferiority to IR-Tac formulations with respect to acute rejection and graft failure outcomes in LDKT."

Pediatrics • Transplant Rejection • Transplantation

Comparison of Immediate- and Extended-Release Tacrolimus Formulations in Deceased-Donor Kidney Transplantation (DDKT) (KIDNEY WEEK 2025) - "Funding Commercial Support – Veloxis Pharmaceuticals, Inc Background Standard maintenance immunosuppression in DDKT typically includes tacrolimus, mycophenolate mofetil (MMF), and ±steroids. In IPW-adjusted Cox models, compared to the Prograf reference group, there were no statistically significant differences in ACGF risk (Generic Tacrolimus: HR=0.95, 95% CI: 0.87–1.02, p =0.17; Envarsus XR: HR=0.90, 95% CI: 0.81–1.00, p =0.06) or in DCGF risk (Generic Tacrolimus: HR=0.95, 95% CI: 0.86–1.05, p =0.35; Envarsus XR: HR=0.93, 95% CI: 0.80–1.09, p =0.40). Conclusion Envarsus XR demonstrates non-inferiority to IR-Tac formulations with respect to acute rejection and graft failure outcomes in DDKT."

Pediatrics • Transplant Rejection • Transplantation

Optimizing Transitions of Care in Kidney Transplantation: The Role of Envarsus XR (KIDNEY WEEK 2025) - "Sponsored by Veloxis Program Description Please join Dr. Allam for a discussion on best practices and emerging strategies to support seamless transitions of care in kidney transplantation with a focus on the role of ENVARSUS XR."

Transplantation

SIMPLE: Simplified IMmunosuppressive Protocol Utilizing Low Dose EnvarsusXR (clinicaltrials.gov) - P4 | N=20 | Terminated | Sponsor: University of Southern California | N=80 ➔ 20 | Recruiting ➔ Terminated; Research contract expired

Enrollment change • Trial termination • Immunology • Transplant Rejection • Transplantation

De-escalated Cyclophosphamide (PTCy) and Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis (clinicaltrials.gov) - P2 | N=56 | Suspended | Sponsor: Medical College of Wisconsin | Trial completion date: Sep 2025 ➔ Sep 2026 | Recruiting ➔ Suspended | Trial primary completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Trial suspension • Graft versus Host Disease • Immunology • Myelodysplastic Syndrome • HLA-B • HLA-C • HLA-DRB1

PTAAK: Pulse Wave Velocity, Tacrolimus Time in Therapeutic Range and CV in African American Kidney Transplants (clinicaltrials.gov) - P4 | N=60 | Active, not recruiting | Sponsor: Roy D. Bloom, MD | Trial completion date: Jan 2026 ➔ May 2026 | Trial primary completion date: Aug 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Transplantation

Veloxis: Phase II Study Evaluating the Efficacy of Tacrolimus Extended Release Tablets to Twice Daily Tacrolimus Dosing Regimen (clinicaltrials.gov) - P2 | N=50 | Completed | Sponsor: Baylor Research Institute | Active, not recruiting ➔ Completed

Trial completion • Immunology • Transplant Rejection • Transplantation

SUPERIOR BIOAVAILABILITY OF TACROLIMUS IN LIVER TRANSPLANT RECIPIENTS TREATED WITH EXTENDED-RELEASE LCP-TACROLIMUS (ENVARSUS) COMPARED TO PROLONGED-RELEASE TACROLIMUS (ADVAGRAF) AFTER 12 WEEKS OF CONTROLLED THERAPY WITHIN A MULTICENTRE, RANDOMISED, CONTROLLED CLINICAL TRIAL ("ENGRAFT") (AASLD 2025) - "Background: Oral tacrolimus formulations exhibit low and variable bioavailability, leading to high dose requirements and dose-dependent toxicities. For the first time in liver transplantation, superior bioavailability of LCPT has been unequivocally demonstrated in a large, multicentre, prospective study statistically powered to test the C/D ratio as a primary endpoint. After the last study visit in October 2026, the final analysis will reconcile drug pharmacokinetics with long-term efficacy and safety data."

Clinical • Movement Disorders • Transplantation

IMPACT OF SWITCH FROM STANDARD-RELEASE TACROLIMUS (PROGRAF®, ADVAGRAF®) TO MELTDOSE® TACROLIMUS (LCPT) (ENVARSUS®) ON HEADACHES/MIGRAINES: THE E-MIG STUDY (AASLD 2025) - "Conversion to Tac-LCP appears to be effective in alleviating Tac-associated neurotoxicity, particularly in patients with headaches and migraines. These findings warrant confirmation in other centers, and a multicenter study is currently underway."

CNS Disorders • Hepatology • Migraine • Movement Disorders • Pain

Comparing Cyclophosphamide and Abatacept With Standard of Care Treatment Following Stem Cell Transplantation (clinicaltrials.gov) - P2 | N=43 | Completed | Sponsor: Dimitrios Tzachanis, MD PhD | Active, not recruiting ➔ Completed

Trial completion • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • Transplantation

Comparison of the Pharmacokinetics of LCP-Tacrolimus (Envarsus®) and Prolonged-Release Tacrolimus (Advagraf®) in Patients with Glomerular Diseases. (PubMed, Nephrol Dial Transplant) - No abstract available

Journal • PK/PD data • Renal Disease

Evaluation of Different Initial Doses of Envarsus in De Novo Kidney Transplant Recipients. (PubMed, J Clin Med) - "Induction therapy included thymoglobulin, sirolimus, and prednisone, with Envarsus initiated once serum creatinine levels fell below 3 mg/dL... An initial dose of 0.08 mg/kg/day resulted in adequate tacrolimus exposure, improved the proportion of patients within the therapeutic range, and minimized unnecessary drug accumulation. These findings suggest that a lower initial dose of Envarsus may be preferable to optimize drug exposure while improving therapeutic precision."

Journal • Transplantation

" SAVE Study (Switch AdVagraf® to Envarsus®) for Fast Metabolizers Kidney Transplant Recipients" (clinicaltrials.gov) - P=N/A | N=226 | Active, not recruiting | Sponsor: Nantes University Hospital | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ May 2026 | Trial primary completion date: Dec 2024 ➔ May 2025

Enrollment closed • Trial completion date • Trial primary completion date • Transplantation