Demonstrated results from a Phase 2, open-label trial that was primarily a PK study and from 12-month safety monitoring in de novo liver transplant patients2,8
Day 4
From Day 4 onwards, the proportion of patients achieving therapeutic trough levels was the same for ENVARSUS® PA as for Prograf®.
Day 7
Therapeutic tacrolimus trough levels (5–20 ng/mL) were achieved by a similar proportion of patients in the ENVARSUS® PA and Prograf® groups, reaching a maximum of 79.3% patients in both treatment groups on Day 7.
As expected for a prolonged-release formulation, the rate at which patients in the ENVARSUS® PA group achieved therapeutic tacrolimus trough levels was initially lower compared with the Prograf® group.
Cumulative rates of patients and graft survival at one year in the mITT analysis (n=58) (secondary endpoints)
- 90.34% ENVARSUS® PA
- 91.10% Prograf®
- p=0.952 for both comparisons
- Overall, four patients died during the study (two in each treatment group), and no other causes of graft loss were observed.
LOW incidence of BPAR seen with ENVARSUS® PA and Prograf® at one year (secondary endpoint)
Number of patients who experienced BPAR episodes by Day 365:
- Six patients ENVARSUS® PA
- Four patients Prograf®
The severity of ENVARSUS® PA BPAR episodes was mostly ≤ Banff Grade 2. The severity of Prograf® BPAR episodes was mostly ≤ Banff Grade 2, with only two patients experiencing BPAR Banff Grade 3.
There was no statistically significant difference in cumulative freedom from BPAR between the ENVARSUS® PA group and the Prograf® group (Day 180: 79.03% vs. 87.00%; Day 365: 73.76% vs. 81.88%).
The incidence of clinically suspected and treated rejection was low (secondary endpoint), with only two patients in the Prograf® group experiencing mild rejection and a further two patients in the Prograf® group experiencing mild steroid-resistant acute rejection.
Overall, there were no significant differences in efficacy and safety
between ENVARSUS® PA once daily and Prograf® twice daily.
Study parameters
Phase 2, open-label, multicentre, randomized trial. Adult de novo liver transplant recipients were randomized to receive ENVARSUS® PA (n=29) once daily with a starting dose of 0.07–0.11 mg/kg/day (0.09–0.13 mg/kg/day Black patients) or Prograf® (n=29) twice daily with a starting dose of 0.10–0.15 mg/kg/day, beginning within 72 hours of reperfusion. Study drug doses were adjusted to maintain target tacrolimus trough levels between 5 and 20 ng/mL. Study 2018 was primarily a PK study and 12-month safety monitoring.
Recommended initial dose indicated for ENVARSUS® PA in de novo liver transplant patients is 0.11–0.13 mg/kg/day.
PK: pharmacokinetic; mITT: modified intent-to-treat; BPAR: biopsy-proven acute rejection
*Comparative clinical significance has not been established.