Everolimus: Additional Phase III data

Additional data from an open-label Phase III trial in 719 de novo liver transplant patients showed that everolimus plus reduced-exposure tacrolimus (3-5 ng/mL) non-significantly reduced the treatment failure rate defined as a composite of death, graft loss or treated biopsy-proven acute rejection at 24 months vs. standard-exposure tacrolimus (6-10 ng/mL) (10.3% vs. 12.5%, p=0.452). Everolimus plus reduced-exposure tacrolimus did significantly reduce the incidence of treated biopsy-proven acute rejection at 24 months vs. standard-exposure tacrolimus alone (6.1% vs. 13.3%, p=0.01). Furthermore, everolimus plus reduced-exposure tacrolimus significantly improved renal failure as measured by the mean difference in eGFR change at 24 months vs. standard-exposure tacrolimus alone (p=0.0018).

A third cohort of patients received everolimus plus reduced-exposure tacrolimus for 4 months followed by everolimus alone. Novartis said enrollment in the tacrolimus withdrawal arm was halted due to a higher incidence of treated biopsy-proven acute rejection episodes and adverse events leading to treatment discontinuation clustered around the time of tacrolimus elimination. Following liver transplant and a 30-day run-in period with tacrolimus, patients were randomized to 1 of the 3 treatment groups. All patients received prednisone. Data were presented at the American Association for the Study of Liver Diseases meeting in Boston. Novartis previously reported that everolimus plus reduced-exposure tacrolimus was non-inferior to standard-exposure tacrolimus alone on the primary endpoint of treatment failure rate at 12 months (6.7% vs. 9.7%, p<0.001 for non-inferiority) (see BioCentury, Feb. 6). ...