Sovaldi (sofosbuvir)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

December of 2013

Specific Treatments:

hepatitis C

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General Information

Sovaldi (sofosbuvir) is a nucleotide analog inhibitor of HCV NS5B polymerase.

Sovaldi is specifically indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen.

Sovaldi is supplied as a tablet for oral administration. The recommended dose is one 400 mg tablet taken once daily with or without food. Sovaldi should be used in combination with ribavirin or in combination with pegylated interferon and ribavirin. Recommended combination therapy and duration is as follows:
Genotype 1 or 4: Sovaldi + peginterferon alfa + ribavirin for 12 weeks
Genotype 2: Sovaldi + ribavirin for 12 weeks
Genotype 3: Sovaldi + ribavirin for 24 weeks.

Clinical Results

FDA Approval
The FDA approval of Solvadi was based on the following clinical trials. The primary endpoint for all trials was the Sustained virologic response (SVR) , defined as HCV RNA less than LLOQ at 12 weeks after the end of treatment.
Genotype 1 or 4 Treatment-Naïve Adults: NEUTRINO (Study 110)
This open label, single arm trial enrolled 327 subjects and evaluated 12 weeks of treatment with Sovaldi in combination with peginterferon alfa 2a and ribavirin. The overall SVR was 90%; Genotype 1:89%, and Genotype 4: 96%.
Genotype 2 or 3 Treatment-Naïve Adults - FISSION (Study 1231)
This randomized, open-label, active-controlled trial enrolled 499 subjects and evaluated 12 weeks of treatment with Sovaldi and ribavirin compared to 24 weeks of treatment with peginterferon alfa 2a and ribavirin. Sovaldi and ribavirin for 12 weeks: the overall SVR was 67%; Genotype 2: 95% and Genotype 3: 56%. Peginterferon alfa 2a and ribavirin for 24 weeks: the overall SVR was 67%; Genotype 2: 78% and Genotype 3: 63%.
Interferon Intolerant, Ineligible or Unwilling Adults - POSITRON (Study 107)
This randomized, double-blinded, placebo-controlled trial enrolled 278 subjects and evaluated 12 weeks of treatment with Sovaldi and ribavirin compared to placebo. Sovladi and RBV for 12 weeks: the overall SVR was 78%. Genotype 2: 93% and Genotype 3: 61% versus 0% for placebo arms.
Previously Treated Adults - FUSION (Study 108)
This randomized, double-blinded trial enrolled 201 subjects and evaluated 12 or 16 weeks of treatment with Sovaldi and ribavirin in subjects who did not achieve SVR with prior interferon-based treatment. Sovaldi and ribavirin for 12 weeks: the overall SVR was 50%. Genotype 2: 82% and Genotype 3: 30%. Sovaldi and ribavirin for 16 weeks: the overall SVR was 71%. Genotype 2: 89% and Genotype 3: 62%.
Treatment-Naïve and Previously Treated Adults - VALENCE (Study 133)
This trial enrolled 419 subjects. It evaluated Sovaldi in combination with weight-based ribavirin for the treatment of genotype 2 or 3 HCV infection in treatment-naïve subjects or subjects who did not achieve SVR with prior interferon-based treatment, including subjects with compensated cirrhosis. The original trial design was a 4 to 1 randomization to Sovaldi + ribavirin for 12 weeks or placebo. Based on emerging data, this trial was unblinded and all genotype 2 HCV-infected subjects continued the original planned treatment and received Sovaldi + ribavirin for 12 weeks, and duration of treatment with Sovaldi + ribavirin in genotype 3 HCV-infected subjects was extended to 24 weeks. Eleven genotype 3 subjects had already completed Solvadi plus ribavirin for 12 weeks at the time of amendment. Genotype 2: Sovaldi plus RBV for 12 weeks; the overall SVR was 93%. Genotype 3: Solvadi plus RBV for 24 weeks; the overall SVR was 84%.

Side Effects

Adverse events associated with the use of Solvadi in combination with ribavirin may include, but are not limited to, the following:

  • fatigue
  • headache

Adverse events associated with the use of Solvadi in combination with peginterferon alfa and ribavirin may include, but are not limited to, the following:
  • fatigue
  • headache
  • nausea
  • insomnia
  • anemia

Mechanism of Action

Sovaldi (sofosbuvir) s an inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA by the NS5B polymerase and acts as a chain terminator.

Additional Information

For additional information regarding Solvadi or hepatitis C, please visit the Sovaldi web page.