Safety and efficacy of treatment with once-daily ledipasvir/sofosbuvir (90/400 mg) for 12 weeks in genotype 1 hcv-infected patients with severe renal impairment.
Lawitz E, Landis CS, Maliakkal BJ, Bonacini M, Ortiz-Lasanta G, Zhang J, Mogalian E, De-Oertel S, Osinusi AO, Brainard DM, McHutchison JG, Flamm SL, Gordon SC, and Gane EJ. Safety and efficacy of treatment with once-daily ledipasvir/sofosbuvir (90/400 mg) for 12 weeks in genotype 1 hcv-infected patients with severe renal impairment. Hepatology 2017; 66:848A-848A.
Background: Despite higher concentrations of the primary circulating sofosbuvir (SOF) metabolite, GS‐331007, in patients with severe renal impairment, retrospective case series and claims database analyses have suggested substantial use of ledipasvir (LDV)/SOF in this population with no untoward effects described. The current study evaluated the safety, efficacy, and pharmacokinetics (PK) of LDV/SOF (90/400 mg) once‐daily for 12 weeks in patients with genotype (GT) 1 HCV‐infection and severe renal impairment. Methods: Treatment naïve or experienced patients with or without compensated cirrhosis and creatinine clearance (CLcr) ≤ 30 mL/min (Cockcroft‐Gault equation), not on dialysis, received open‐label treatment with LDV/SOF once daily for 12 weeks. Virologic response, pharmacokinetics (PK), and safety, including echocardiograms, were assessed. Results: Of the 18 patients enrolled and treated, the majority were male (67%), 10 (56%) were African‐American, 8 (44%) had BMI >30 kg/ m2 and mean (range) CLcr at baseline was 24 9 (9 0‐39 6) mL/min. In terms of liver disease characteristics, all 18 had GT1 HCV infection (14 GT1a and 4 GT1b), 14 (78%) were treatment naïve, and 2 (11%) had cirrhosis. All patients completed 12 weeks of LDV/SOF treatment. There were no early discontinuations nor any on‐treatment virologic failures. The SVR4 rate is 100% (18/18). Preliminary PK data in subjects with severe renal impairment demonstrate that the exposure of SOF and GS‐331007 were approximately 2.6‐ and 5.1‐fold higher, respectively, than in subjects in the LDV/SOF Phase 3 studies; LDV exposure was similar in both populations. The most common adverse events (AEs) were fatigue (22%), headache (22%), and hyperkalemia (22%). Six serious AEs were reported among 4 patients (22%), including 2 renal events; no SAEs were considered related to study drugs. Preliminary analysis of echocardiogram data from the first 8 subjects demonstrated stable parameters from screening through the end of treatment. Complete SVR12, PK, and echocardiogram results will be presented. Conclusions: Treatment with LDV/SOF (90/400 mg) for 12 weeks in genotype 1 patients with and without cirrhosis and severe renal impairment resulted in 100% SVR4 rate. The regimen was safe and well‐tolerated with no treatment discontinuations and no treatment‐related SAEs.