Veloxis Pharmaceuticals’ once-daily Envarsus® XR (tacrolimus extended-release tablets), an investigational new drug under FDA review for the prevention of organ rejection in adult kidney transplant patients, demonstrated that a lower, once-a-day dose of Envarsus XR in African-American kidney transplant patients is sufficient to achieve therapeutic tacrolimus blood concentrations, compared to twice-daily immediate release tacrolimus.
The results, from one of the largest trials of tacrolimus pharmacokinetics (PK) in African-American kidney transplant patients conducted to date, were presented at the American Transplant Congress (ATC) on May 3 in Philadelphia. The presentation was entitled “PK and Pharmacogenomics of Once-daily MeltDose® Tacrolimus (Envarsus® XR) vs. Twice-daily Tacrolimus: A Randomized Cross-over Study in Stable African-American Kidney Transplant Patients (ASERTAA).”
African-Americans can be a challenging patient population for managing immune suppression, with historically poorer outcomes. Expression of the CYP3A5*1 genotype, which codes for a cytochrome p450 enzyme that metabolizes tacrolimus, was shown to be present in approximately 80 percent of African-Americans and that genotype commonly requires higher tacrolimus doses to obtain and maintain therapeutic levels of tacrolimus. Higher tacrolimus dosing has the potential to increase the risk of tacrolimus-associated adverse events. This study evaluated the PK profile of once-daily Envarsus® XR compared to twice-daily or immediate-release tacrolimus (IR-Tac) in this patient population.
The optimal conversion ratio for once-daily extended release Envarsus XR was shown to be approximately 20 percent lower than the total IR-Tac. Peak tacrolimus concentration (Cmax) was reduced 30 percent for patients on Envarsus while intra-day fluctuation was reduced 50 percent.
Conversion of African-American patients from IR-Tac to Envarsus XR was demonstrated to be readily achieved with a reduction in dose of approximately 20 percent without concern for genotype status.
“The data seen in this study suggest that African-American patients treated with Envarsus are able to reliably achieve adequate blood levels at a lower dose than with traditional immediate-release tacrolimus and that they will not experience as high a peak blood level during the day,” said Roy D. Bloom, M.D., Professor of Medicine, University of Pennsylvania and Medical Director of the Penn Kidney Pancreas Transplant Program. “Envarsus may offer an important additional therapeutic option in our management of this traditionally hard-to-treat transplant population.”