Terms used in these reports:
- RVR (Rapid virological response)= No virus detected at week 4
- eRVR(Extended rapid virological response) = No virus detected at week 4 and week 12
- EVR (Early Virological Response) — 2 log drop of HCV RNA after 12 weeks.
- cEVR = Complete Early Virological Response — No virus detected after 12 Weeks.
- SVR12 (Sustained virological response) = No virus detected at 12 weeks after completion of treatment.
- SVR24 = No virus detected at 24 weeks after completion of treatment.
In January 2014 the European Commission approved Sovaldi (from Gilead) and it was launched in the U.K., Germany, and France. This is the first of the newer generation of drugs to be approved and we believe that many will follow over the next couple of years.
Approval of Sovaldi (sofosbuvir) tablets for the treatment of chronic hepatitis C
On December 6, 2013, FDA approved SOVALDI (sofosbuvir) tablets for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen.
Sovaldi is the first drug that has demonstrated safety and efficacy to treat certain types of HCV infection without the need for co-administration of interferon, andis the second drug approved by the FDA in the past two weeks to treat chronic HCV infection. On November 22, the FDA approved Olysio (simeprevir)..
Below is a summary of the basis of approval and highlights from the prescribing information for Sovaldi. Please refer to the full prescribing information for all the information needed to use Sovaldi safely and effectively.
INDICATIONS AND USAGE
SOVALDI is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor indicated for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen.
SOVALDI efficacy has been established in subjects with HCV genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection
The following points should be considered when initiating treatment with SOVALDI:
Monotherapy of SOVALDI is not recommended for treatment of CHC.
Treatment regimen and duration are dependent on both viral genotype and patient population
Treatment response varies based on baseline host and viral factors
DOSAGE AND ADMINISTRATION
The recommended dose of SOVALDI is one 400 mg tablet, taken orally, once daily with or without food
SOVALDI should be used in combination with ribavirin or in combination with pegylated interferon and ribavirin for the treatment of CHC in adults. The recommended regimen and treatment duration for SOVALDI combination therapy is provided in Table 1.
Table 1 Recommended Regimens and Treatment Duration for SOVALDI Combination Therapy in HCV Mono-infected and HCV/HIV-1 Co-infected Patients
Treatment Duration Patients with genotype 1 or 4 CHC SOVALDI + peginterferon alfaa + ribavirinb 12 weeks Patients with genotype 2 CHC SOVALDI + ribavirinb 12 weeks Patients with genotype 3 CHC SOVALDI + ribavirinb 24 weeks
a. See peginterferon alfa prescribing information for dosing recommendation for patients with genotype 1 or 4 CHC.
b. Dose of ribavirin is weight-based (<75 kg = 1000 mg and ≥75 kg = 1200 mg). The daily dose of ribavirin is administered orally in two divided doses with food. Patients with renal impairment (CrCl ≤ 50 mL/min) require ribavirin dose reduction; refer to ribavirin prescribing information.
SOVALDI in combination with ribavirin for 24 weeks can be considered as a therapeutic option for CHC patients with genotype 1 infection who are ineligible to receive an interferon-based regimen. Treatment decision should be guided by an assessment of the potential benefits and risks for the individual patient.< p/>
Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation
SOVALDI in combination with ribavirin is recommended for up to 48 weeks or until the time of liver transplantation, whichever occurs first, to prevent post-transplant HCV reinfection.
Severe Renal Impairment and End Stage Renal Disease
No dose recommendation can be given for patients with severe renal impairment (estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73m2) or with end stage renal disease (ESRD) due to higher exposures (up to 20-fold) of the predominant sofosbuvir metabolite.
WARNINGS AND PRECAUTIONS
Use with Potent P-gp Inducers
Drugs that are potent P-gp inducers in the intestine (e.g., rifampin, St. John’s wort) may significantly decrease sofosbuvir plasma concentrations and may lead to a reduced therapeutic effect of SOVALDI. Rifampin and St. John’s wort should not be used with SOVALDI.
The most common adverse events (≥ 20%) for SOVALDI + ribavirin combination therapy were fatigue and headache. The most common adverse events (≥ 20%) for SOVALDI + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia and anemia.