Used to treat chronic hepatitis C genotype 1 infection in adults.
The first once-daily single tablet regimen for the treatment of Genotype 1 chronic hepatitis C.
Achieves cure rates of 94-99 percent in 3 Phase 3 studies.
Shortens treatment duration to 8 weeks for some treatment naïve patients.
Eliminates the need for treatment with interferon and ribavirin in patients with Genotype 1 hepatitis C.
Ledipasvir 90 mg/sofosbuvir 400 mg dosage.
Combines the NS5A inhibitor ledipasvir with the nucleotide analog polymerase inhibitor sofosbuvir.
Treatment duration of eight, 12 or 24 weeks depending on prior treatment history, cirrhosis status and baseline viral load.
Eight weeks of treatment can be considered for treatment-naïve patients without cirrhosis who have baseline HCV viral load below 6 million IU/mL.
The drug’s approval is supported by data from three Phase 3 studies, ION-1, ION-2 and ION-3.
These ION studies evaluated eight, 12 or 24 weeks of treatment with Harvoni, with or without ribavirin, among nearly 2,000 genotype 1 HCV patients with compensated liver disease.
These studies included non-cirrhotic treatment-naïve patients (ION-3), cirrhotic and non-cirrhotic treatment-naïve patients (ION-1) and cirrhotic and non-cirrhotic patients who failed prior therapy with an interferon-based regimen, including regimens containing an HCV protease inhibitor (ION-2).
The primary endpoint for each study was sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12).
In the above studies ribavirin was not shown to increase response rates.
Trial participants in the ribavirin-free arms achieved SVR12 rates of 94 to 99 percent.
The most common adverse reactions are: fatigue, headache, nausea, diarrhea and insomnia.
Rifampin and St. John’s wort may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
Coadministration with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir can decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of the drug..
Coadministration isnot recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir.
In co-infected HIV and hepatitis C patients Ledipasvir plus Sofosbuvir associated with SVR of 98% (Osinuri A et al).
Coadministration is not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.