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

Physician-Reported Satisfaction with, Challenges in, and Patient Adherence to, Immunosuppressive Treatment among Kidney Transplant Recipients: Results From a Real-World Survey (ISPOR 2025) - "The most frequently prescribed immunosuppressants were tacrolimus (70% of patients), mycophenolate mofetil (63%) and corticosteroids (59%)... Overall, physician satisfaction with prescribed therapy was high, however, for approximately a third of patients, challenges relating to side effects and treatment adherence were reported. Further research is needed to understand the impact of side effects and non-adherence on both clinical and patient-reported outcomes."

Adherence • Clinical • Real-world • Real-world evidence • Cardiovascular • Movement Disorders • Nephrology • Transplantation

Comparison of Early Conversion to LCP-Tacrolimus (ENVARSUS XR) to Immediate-Release Tacrolimus in Lung Transplant Recipients. (PubMed, Clin Transplant) - P2 | "In conclusion, early conversion to LCPT was feasible and similarly efficacious to IRT in a cohort of lung transplant recipients. Trial Registration: ClinicalTrials.gov identifier: NCT04420195."

Journal • Antibody-mediated Rejection • Chronic Kidney Disease • Immunology • Nephrology • Respiratory Diseases • Transplant Rejection • Transplantation

CIRTEN SPK: CIRTEN-Simultaneous Pancreas-Kidney Transplant Recipients (clinicaltrials.gov) - P2/3 | N=20 | Recruiting | Sponsor: University of Wisconsin, Madison | N=30 ➔ 20 | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Enrollment change • HEOR • Trial completion date • Trial primary completion date • Hepatology • Transplantation

EVITRA: Extended Release Versus Immediate Release Tacrolimus Following Renal Allograft Failure to Reduce Allosensitisation (clinicaltrials.gov) - P4 | N=35 | Terminated | Sponsor: Imperial College Healthcare NHS Trust | N=64 ➔ 35 | Trial completion date: Nov 2023 ➔ Feb 2025 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2021 ➔ Jun 2024; Non-feasible due to change in clinical practice

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Transplantation

Drug Interaction With Envarsus XR and Grapefruit Juice (clinicaltrials.gov) - P=N/A | N=11 | Completed | Sponsor: Shirley M. Tsunoda | N=20 ➔ 11 | Unknown status ➔ Completed

Enrollment change • Trial completion • Transplantation

Conversion from Twice Daily Tacrolimus to LCP-Tacrolimus (Envarsus XR®) in Pediatric Lung Transplant Recipients at a Tertiary Institution (ISHLT 2025) - "CF patients required a higher conversion ratio to reach their goal tacrolimus level. Further studies should look at long-term outcomes on allograft and kidneys, as well as quality of life and adherence measurements."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Pain • Pediatrics • Respiratory Diseases • 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 primary completion date: Mar 2025 ➔ Mar 2026

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

Evaluation of Anti-rejection Drug, Tacrolimus, in African-Americans with Kidney Transplant (clinicaltrials.gov) - P4 | N=46 | Active, not recruiting | Sponsor: The Methodist Hospital Research Institute | Withdrawn ➔ Active, not recruiting | Trial completion date: Oct 2022 ➔ Oct 2025 | Trial primary completion date: Oct 2020 ➔ Jul 2025

Enrollment closed • Trial completion date • Trial primary completion date • Nephrology • Renal Disease • Transplant Rejection • Transplantation

Early Use of Long-acting Tacrolimus in Lung Transplant Recipients (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Vanderbilt University Medical Center | Enrolling by invitation ➔ Recruiting

Enrollment status • Transplantation

TARGET: Tacrolimus and Risk Factors for Glucose Metabolism Disorders in Kidney Transplant Patients (clinicaltrials.gov) - P=N/A | N=120 | Not yet recruiting | Sponsor: Chiesi Poland Sp. z o.o.

New trial • Metabolic Disorders • Renal Disease • Transplantation

OPERATOR: Cognitive Outcomes in Stable Renal Transplant Patients Switched FromTacrolimus to Envarsus XR™ (clinicaltrials.gov) - P4 | N=60 | Active, not recruiting | Sponsor: Vanderbilt University Medical Center | Trial completion date: Dec 2024 ➔ Jan 2026 | Trial primary completion date: Dec 2024 ➔ Jan 2026

HEOR • Trial completion date • Trial primary completion date • Transplantation

Experience in the use of MeltDose tacrolimus in paediatric kidney transplantation. Single-center retrospective study (IPNA 2025) - "MeltDose formulation (LCP-TAC, Envarsus®) has demonstrated similar efficacy and safety compared to immediate-release tacrolimus (IR-TAC, Prograf®) and extended-release tacrolimus (ER-TAC, Advagraf®), greater bioavailability and better pharmacokinetics. No other notable complications were observed. Conclusions LCP-TAC seems to be a safe formulation in paediatrics and could provide a better pharmacokinetic profile, especially in children with high intra-individual variability."

Retrospective data • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Pediatrics • Renal Disease • Transplantation

Measurement of Whole Blood Tacrolimus Concentrations by LC-MS/MS and Immunoassay Methods: Influence of Immediate-Release vs Extended-Release Tacrolimus Formulations. (PubMed, J Appl Lab Med) - "Biases between immunoassay and LC-MS/MS tacrolimus measurements in patients receiving immediate-release vs extended-release formulations indicate that their distinct pharmacokinetic profiles impact measurement accuracy. These assay biases should be considered when interpreting tacrolimus concentration measurements."

Journal

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

New P4 trial • Transplantation

Conversion from tacrolimus IR to LCP Envarsus requires significant therapeutic drug level monitoring (ASHP 2024) - No abstract available

A Global Comparison of Liver Transplant Drug Pricing: US vs the G7 Countries and Australia (ACG 2024) - " Publicly available drug formularies for Canada, UK, Japan, France, Germany, Italy, and Australia were used to collect 2024 prices for 8 commonly used liver transplant immunosuppressive medications (mycophenolate mofetil, mycophenolate sodium, sirolimus, tacrolimus, Advagraf®, Envarsus®, everolimus, & cyclosporine). U.S. originator prices for liver transplant medications were on average 4.84x the prices in G7 countries and Australia. At its lowest dose, mycophenolate mofetil costs $10.80 in the U.S. with the price range of $0.56-$2.68 among comparison countries. Similarly, mycophenolate sodium costs $8.14 in the U.S. compared to $0.97-$1.73 globally, sirolimus $20.63 vs."

Clinical • Pricing • Hepatology • Transplantation

Chronic Diarrhea Secondary to Collagenous Colitis in a Kidney Transplant Recipient (ACG 2024) - "Budesonide can promptly resolve symptoms for these patients...Her immunosuppression included Envarsus, Myfortic, and prednisone...It is important to identify MC early as the treatment can improve the quality of life for patients. Our case study highlights the importance to keep a low threshold for MC as the cause of diarrhea and concurrent gastrointestinal symptoms in this patient population."

Clinical • Acute Kidney Injury • Cardiovascular • Diabetes • Diabetic Nephropathy • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hypertension • Immunology • Inflammation • Leukopenia • Metabolic Disorders • Nephrology • Pain • Renal Disease • Solid Organ Transplantation • Transplantation • Type 2 Diabetes Mellitus

Transitions of Care in Kidney Transplant with ENVARSUS XR® (KIDNEY WEEK 2024) - "Sponsored by Veloxis Pharmaceuticals"

Transplantation

SIMPLE: Envarsus XR Compared to Immediate Release Tacrolimus (clinicaltrials.gov) - P4 | N=240 | Active, not recruiting | Sponsor: Mayo Clinic | Trial completion date: Jul 2024 ➔ Jul 2025 | Trial primary completion date: Jul 2024 ➔ Jul 2025

Adherence • Trial completion date • Trial primary completion date • Transplantation

Evaluation of Effective Half-Life and Its Impact on Time to Steady State for Oral MeltDose Tacrolimus (LCPT) in De Novo Kidney Transplant Recipients. (PubMed, Ther Drug Monit) - "Consistent with its prolonged release of tacrolimus, LCPT demonstrated a higher accumulation ratio and a longer t1/2eff compared with IR-Tac. These findings underscore the pharmacokinetic differences between different drug formulations of the same moiety and may help inform dose adjustments for LCPT in kidney transplantation."

Journal • Transplantation

Effects of switching from twice-daily tacrolimus to once-daily extended-release meltdose tacrolimus on cellular immune response. (PubMed, Front Transplant) - "LCP-Tacro [LCPT], a novel once-daily, extended-release formulation of tacrolimus, has a reduced Cmax with comparable AUC exposure, requiring a ∼30% dose reduction in contrast to immediate-release tacrolimus (IR-Tac)...Here, we demonstrate first insights into the immune system changes occurred under IR-Tac to LCPT conversion therapy in kidney transplant patients. While phenotypic and functional characteristics of the most immune cell populations did not change, we could observe an a transient expansion of regulatory T cells in peripheral blood following IR-Tac to LCTP conversion, which might additionally contribute to the overall immunosuppressive effect."

Journal • Infectious Disease • Tetanus • Transplantation

Utilization Of Extended Release Tacrolimus Formulations For Cardiac Transplant Recipients In The United States; A 10-year Retrospective (HFSA 2024) - "Several tacrolimus formulations are available in the US, including twice-daily immediate-release (“Tacrolimus IR”; generic or Prograf), once-daily extended-release (“Tacrolimus ER”; Astagraf XL), and a novel once-daily extended release (“Tacrolimus LCP”; Envarsus XR)...Cyclosporine was not used in this cohort...Several tacrolimus formulations are available in the US, including twice-daily immediate-release (“Tacrolimus IR”; generic or Prograf), once-daily extended-release (“Tacrolimus ER”; Astagraf XL), and a novel once-daily extended release (“Tacrolimus LCP”; Envarsus XR)...Cyclosporine was not used in this cohort...Among those treated with tacrolimus there were no significant di"erences in survival by formulation type. Conclusion Despite theoretical benefits of once-daily extended release tacrolimus formulations and their apparent safety, their utilization in the US over the last decade has been modest."

Retrospective data • Transplantation

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

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

Experience in the use of MeltDose tacrolimus in paediatric kidney transplantation. Single-center retrospective study (ESPN 2024) - "MeltDose formulation (LCP-TAC, Envarsus®) has demonstrated similar efficacy and safety compared to immediate-release tacrolimus (IR-TAC, Prograf®) and extended-release tacrolimus (ER-TAC, Advagraf®), greater bioavailability and better pharmacokinetics. LCP-TAC seems to be a safe formulation in paediatrics and could provide a better pharmacokinetic profile, especially in children with high intra-individual variability."

Retrospective data • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Pediatrics • Renal Disease • Transplantation

OPERATOR: Cognitive Outcomes in Stable Renal Transplant Patients Switched fromTacrolimus to Envarsus XR™ (clinicaltrials.gov) - P4 | N=60 | Active, not recruiting | Sponsor: Vanderbilt University Medical Center | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

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