The FDA approved changes to the product labels for direct-acting antivirals Harvoni, Epclusa, and Vosevi to include new efficacy and safety data for adults with hepatitis C and severe renal impairment, including those who require dialysis.
“The product labeling updates for Epclusa, Harvoni and Vosevi recognize the high unmet need for effective HCV treatments for patients with severe renal impairment, including those with end stage renal disease (ESRD) who are on dialysis,” Gilead said in a statement sent to Healio Gastroenterology and Liver Disease. “People with chronic HCV who are on dialysis as a result of ESRD have an increased risk of morbidity and mortality. Prior HCV treatment options for this population have been associated with clinical barriers resulting in continued unmet medical need, and these approvals provide important new options for these patients.”
Harvoni (sofosbuvir/ledipasvir, Gilead Sciences) required no dosage adjustment for patients with mild, moderate or severe renal impairment including end-stage renal disease. The most common adverse events among patients with ESRD were insomnia and headache.
In a trial of adults with chronic HCV and ESRD requiring dialysis, the sustained virologic response was 93% in 45 treatment-naive patients who received 8 weeks of sofosbuvir/ledipasvir, 100% in 12 patients who received 12 weeks of treatment, and 83% in six treatment-experienced patients with cirrhosis who received 24 weeks of treatment.
Similarly, Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) required no dosage adjustment for any degree of renal impairment and the most common adverse event among patients with ESRD was nausea.
Results from a trial of 59 patients with HCV and ESRD requiring dialysis showed an overall SVR rate of 95% after 12 weeks of treatment with sofosbuvir/velpatasvir, including patients with cirrhosis (29%) and those who were treatment-experienced (22%).
Vosevi (sofosbuvir/velpatasvir/voxilaprevir or SOF/VEL/VOX, Gilead Sciences) also required no dosage adjustment for any degree of renal impairment.
Pharmacokinetics of sofosbuvir and velpatasvir among patients with HCV and ESRD requiring dialysis for 12 weeks were consistent with patients with ESRD without HCV. The pharmacokinetics of voxilaprevir have not been studied in patients with ESRD; however, the FDA noted that voxilaprevir exposure following treatment with SOF/VEL/VOX combination is not expected to be meaningfully altered in patients with HCV and ESRD requiring dialysis compared with patients with normal renal function.