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

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

Extended-Release Tacrolimus Following Liver Transplantation (clinicaltrials.gov) - P4 | N=94 | Recruiting | Sponsor: University of Alberta | Trial primary completion date: Jul 2025 ➔ Dec 2026

Trial primary completion date • Cardiovascular • Metabolic Disorders • Nephrology • Renal Disease • 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") (WTC 2025) - "*Purpose: 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. The last study visit is projected for October 2026, after which the final trial analysis will reconcile drug pharmacokinetics with long-term efficacy and safety data."

Clinical • Movement Disorders • Transplant Rejection • Transplantation

Subcutaneous Administration of a CD28 Co-Stimulation Blocker Demonstrates Efficacy in an NHP Model of Kidney Allotransplantation (WTC 2025) - "Unlike CD80/86 blocking with belatacept, direct CD28 blocking with VEL-101 prevents T-cell activation while preserving important immunoregulatory CD80/86-CTLA4 and CD80-PD-L1 interactions. This study tests efficacy of a clinically relevant drug regimen.* Life-sustaining kidney transplants were performed in MHC mismatched Rhesus macaques (RM) randomly assigned to 4 treatment groups (n=5 per group) -- Group 1: subcutaneous (SQ) VEL-101 monotherapy, Group 2: SQ VEL‑101 combined with standard-of-care (SOC; huATG induction, mycophenolate mofetil (MMF), and methylprednisolone), Group 3: no IS controls (2 current, 3 historical), and Group 4: tacrolimus combined with SOC... SQ VEL-101 demonstrates efficacy in preventing rejection after life-sustaining kidney transplant in NHPs. VEL-101 with SOC demonstrated comparable RFS to SOC with tacrolimus while eliciting less donor specific antibody and avoiding the sequelae of CNI-based IS."

Clinical • Transplantation • CD80 • CTLA4 • PD-L1

Different Immuno-Profiles on Renal Transplant Recipients under Extended vs. Standard Release Tacrolimus; Results from a Randomized Controlled Trial (WTC 2025) - "We aimed to compare differences in immune-profile of patients undergoing kidney transplantation using extended-release Tacrolimus (Envarsus XR, ENV), vs traditional twice daily Tacrolimus (standard)... Our results support the immunological advantage of renal transplant patients under ENV compared to those taking standard Tacrolimus regimen."

Clinical • Solid Organ Transplantation • Transplantation • CD4 • CD8 • IL2

Cognitive Outcomes and Quality of Life in Stable Renal Transplant Patients Switched from Twice-Daily Tacrolimus to Envarsus XRTM (WTC 2025) - "Kidney transplant patients converted from IR tacrolimus to LCP-Tacro led to statistically significant benefits in cognitive function including visual attention, executive functioning, and memory."

Clinical • HEOR • Late-breaking abstract • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Insomnia • Movement Disorders • Post-traumatic Stress Disorder • Sleep Disorder • Solid Tumor • Transplantation

Final Results of the Protection of Renal Function After Conversion of Fast IR-Tac Metabolizers to Envarsus Study (The Protect RENvarusus Study) (WTC 2025) - "The Tac C/D ratio should be calculated early after RTx in order to identify patients at risk. Fast Tac metabolizers in particular benefit from the noticeable dose reduction after switching to LCP-Tac."

Clinical • Infectious Disease • Transplant Rejection

The Low-Intensity Conditioning Regimen with Fludarabine Achieved Mixed Chimerism and Minimization of Immunosuppression without Cytokine Release Syndrome (WTC 2025) - "The conditioning regimen included cyclophosphamide, fludarabine, anti-CD2 mAb, rituximab, thymic irradiation and tacrolimus monotherapy (Fig...With additional rituximab, the allografts remained stable on Envarsus, with or without belatacept... The revised conditioning regimen with fludarabine effectively induced mixed chimerism while significantly reducing the incidence and severity of CRS compared to the previous regimen. Among recipients reaching 12 months post-transplant, 6 of 7 achieved IS minimization. However, HLA-full mismatched recipients faced greater challenges in IS tapering, highlighting the need for further optimization of the conditioning regimen."

Cytokine release syndrome • Acute Kidney Injury • Bone Marrow Transplantation • Inflammation • Nephrology • Solid Organ Transplantation

Clinical Factors Influencing Tacrolimus Metabolism and Blood Level Early After Kidney Transplantation-A Comparison of Three Different Tacrolimus Formulations. (PubMed, J Clin Med) - "In patients treated with Advagraf, eGFR (rpartial = 0.291; p < 0.05), antithymocyte globulin (vs. basiliximab) induction (rpartial = 0.445; p < 0.001), lipopolysaccharide (LPS) level (rpartial = 0.393; p < 0.01) and drug dose (rpartial = 0.433; p < 0.01) were independently associated with tacrolimus AUC. We confirmed the significant association between markers of intestinal permeability and tacrolimus exposure in KTRs who underwent early post-transplant conversion from Prograf to Advagraf or Envarsus. This may suggest that the planned tacrolimus conversion from the twice-daily to the once-daily formulation should be performed later (at least 3 months after transplantation) to avoid unnecessary tacrolimus blood level instability."

Journal • Transplantation

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

Enrollment open • Metabolic Disorders • Renal Disease • Transplantation