The Clinical Development of Ledipasvir/Sofosbuvir (LDV/SOF, Harvoni®)

Abstract

The fixed-dose combination tablet of ledipasvir (LDV), an HCV NS5A inhibitor, and sofosbuvir (SOF), an HCV nucleotide analog NS5B polymerase inhibitor, was the first all-oral (one-pill once daily), interferon-free and ribavirin-free regimen approved for the treatment of patients with chronic hepatitis C. With over 5,900 HCV-infected patients enrolled in LDV/SOF clinical trials through late 2017, the accelerated clinical development program was able to generate safety and efficacy data across a broad range of patient populations. The initial registration trials demonstrated that 12 weeks of treatment with LDV/SOF resulted in high cure rates of over 95% in HCV genotype 1 patients regardless of historical negative treatment predictors including cirrhosis or prior treatment history. The program subsequently expanded to include other HCV genotypes and special populations with significant unmet medical need including but not limited to decompensated liver disease, HIV/HCV coinfection, posttransplantation, and children. With favorable pharmacokinetic properties, good safety profile, and high efficacy rates, the approval of LDV/SOF (Harvoni®) ushered in a new era of treatment and management for the millions of HCV-infected patients globally.