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Gilead Files NDA for HCV Combination Therapy

March 1, 2014

Gilead Sciences filed a New Drug Application (NDA) with the US Food and Drug Administration (FDA) for ledipasvir (LDV)/sofosbuvir (SOF), a fixed-dose combination therapy for genotype 1 hepatitis C infection (HCV). Both drugs are direct-acting antivirals. LDV is an NS5A inhibitor, a drug that disrupts nonstructural (NS) proteins HCV needs to replicate. SOF is a nucleotide analog polymerase inhibitor, which blocks polymerase, an enzyme that provides instructions for making copies of HCV RNA.

Genotype 1 is especially difficult to treat, accounting for approximately 75% of HCV patients in the US. The therapy excludes the use of the existing standard of treatment for HCV--weekly injections of pegylated interferon (peg-IFN) and a daily ribavirin (RBV) oral pill. This regimen is not ideal, as nearly 50% of patients do not respond to it. In addition, those who do respond often experience debilitating side effects that can last the duration of the treatment—either 24 or 48 weeks. Pharmaceutical companies are experimenting with interferon-free regimens to see if they can eliminate some of the severe side effects.

The NDA was submitted after three phase III studies (ION-1, ION-2 and ION-3) in which nearly 2,000 genotype 1 HCV patients received LDV/SOF therapy either with or without RBV for eight, 12 or 24 weeks. Trial participants included individuals who were treatment-naïve or who had failed previous treatment, including protease inhibitor-based regimens, and those with compensated cirrhosis. Supporting data included in the NDA recommends the use of LDV/SOF in treatment duration of eight or 12 weeks, depending on patients’ prior treatment history and whether they are cirrhosis positive.

“Today’s filing brings us one step closer to our goal of offering all patients with hepatitis C a simple, safe and highly effective all-oral treatment regimen,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer. “Based on the data from the Phase 3 ION studies, the LDV/SOF combination may have the potential to cure HCV in genotype 1 patients in as little as eight weeks and without the need for interferon injections or ribavirin.”


Source: Gilead press release dated February 10, 2014