Sofosbuvir (brand name Sovaldi) is a nucleotide analog used in combination with other drugs for the treatment of hepatitis C virus (HCV) infection. It has been marketed since 2013. Compared to previous treatments, sofosbuvir-based regimens provide a higher cure rate, fewer side effects, and a two- to four-fold reduced duration of therapy. Sofosbuvir allows most patients to be treated successfully without the use of peginterferon, an injectable drug with severe side effects that is a key component of older drug combinations for the treatment of HCV.
Sofosbuvir inhibits the RNA polymerase that the hepatitis C virus uses to replicate its RNA. It was discovered at Pharmasset and developed by Gilead Sciences.
In 2013, the FDA approved sofosbuvir in combination with ribavirin (RBV) for oral dual therapy of HCV genotypes 2 and 3, and for triple therapy with injected pegylated interferon (pegIFN) and RBV for treatment-naive patients with HCV genotypes 1 and 4. In 2014 a combination of sofosbuvir with the viral NS5A inhibitor ledipasvir was approved. This latter combination provides high cure rates in people infected with genotype 1 (the most common subtype in the U.S., Japan, and much of Europe) without the use of interferon, irrespective of prior treatment failure or the presence of cirrhosis.
The price of sofosbuvir, quoted in various media sources as $84,000 to $168,000 for a course of treatment in the U.S., £35,000 in the UK for 12 weeks has engendered considerable controversy.
FDA Status: On December 6, 2013, sofosbuvir received approval from the U.S. FDA for treatment of individuals with chronic hepatitis C as a component of combination therapy.
On November 5, 2014, the U.S. FDA approved the use of simeprevir in combination with sofosbuvir for patients with genotype 1 chronic hepatitis C infection.
On July 24, 2015, the U.S. FDA approved the use of daclatasvir in combination with sofosbuvir for patients with genotype 3 chronic hepatitis C infection.
Indications: The following indications for sofosbuvir relate to patients with chronic hepatitis C virus infection.
Sofosbuvir is indicated for treatment of patients with HCV monoinfection and HCV/HIV-1 coinfection
Genotype 1 or 4: sofosbuvir plus peginterferon-alfa plus ribavirin for 12 weeks
Genotype 2: sofosbuvir plus ribavirin for 12 weeks
Genotype 3: sofosbuvir plus ribavirin for 24 weeks
Genotype 1, interferon ineligible: sofosbuvir plus ribavirin can be considered for 24 weeks in patients who are interferon ineligible
Sofosbuvir for patients with chronic HCV monoinfection
Genotype 1 and not eligible for interferon: sofosbuvir plus ribavirin for 24 weeks can be considered
Hepatocellular carcinoma awaiting liver transplantation: sofosbuvir plus ribavirin for a duration of up to 48 weeks or until liver transplantation, whichever occurs first, to prevent post-transplant HCV reinfection
Simeprevir in Combination with Sofosbuvir for HCV Infection:
Genotype 1: Treatment-naive or treatment experienced patients without cirrhosis: 12 weeks of simeprevir and sofosbuvir
Genotype 1: Treatment-naive or treatment experienced patients with cirrhosis: 24 weeks of simeprevir and sofosbuvir
Daclatasvir in Combination with Sofosbuvir for HCV Infection:
Genotype 3: Treatment-naive or treatment experienced patients without cirrhosis: 12 weeks of daclatasvir and sofosbuvir
Genotype 3: Treatment-naive or treatment experienced patients with cirrhosis: the optimal duration of therapy with daclatasvir and sofosbuvir remains unknown
Dosing: Sofosbuvir is available as a 400 mg tablet1. The recommended dose of sofosbuvir is 400 mg taken orally once daily, with or without food. The 400 mg dose of sofosbuvir should be used, regardless of the patient’s genotype and prior hepatitis C treatment experience. No dose adjustment is needed for mild-to-moderate renal impairment or with mild, moderate, or severe hepatic impairment. The prescribing information does not make a recommendation for dosing in patients who have severe renal impairment (eGFR less than 30 ml/min/1.73m2) or end stage renal disease requiring dialysis. Sofosbuvir is under study with the NS5A inhibitor ledipasvir as a fixed-dose combination pill (ledipasvir 90 mg and sofosbuvir 400 mg) taken once daily.