Gilead Sciences, Inc, a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need, announced results from two studies evaluating the safety and efficacy of investigational uses of sofosbuvir-based regimens in chronic hepatitis C virus (HCV)-infected patients with genotypes 2, 3, 4 and 5.

Results from the BOSON study of Sovaldi (sofosbuvir 400 mg) in combination with ribavirin (RBV) or with pegylated interferon (PEG)/RBV demonstrated high cure rates across all patients with genotypes 2 and 3.

Separately, results from a phase 2 study demonstrate the safety and efficacy of Harvoni (ledipasvir 90 mg/sofosbuvir 400 mg) in patients with genotypes 4 or 5 infection.

Data from both studies will be presented in oral sessions at the 50th annual meeting of the European Association for the Study of the Liver (The International Liver Congress 2015) in Vienna, Austria.

Sovaldi and Harvoni are each approved in the United States for the treatment of chronic HCV infection. Sovaldi is used in combination with other agents and its efficacy has been established in patients with genotypes 1-4; Harvoni is indicated for patients with genotype 1.

BOSON (Study GS-US-334-0153, #LB05), a randomised phase 3 study of 592 patients, evaluated the safety and efficacy of Sovaldi plus RBV for 16 or 24 weeks compared with Sovaldi plus PEG/RBV for 12 weeks among treatment-naïve or treatment-experienced genotype 3 patients with and without cirrhosis and treatment-experienced genotype 2 patients with cirrhosis. Thirty-seven percent of study participants had cirrhosis.



Among genotype 3 patients, rates of sustained virologic response 12 weeks after treatment (SVR12) were highest among those receiving Sovaldi plus PEG/RBV for 12 weeks (93 per cent, n=168/181), compared to those receiving Sovaldi plus RBV for 24 weeks (84 per cent, n=153/182) or for 16 weeks (71 per cent, n=128/181). Treatment-experienced genotype 3 patients with cirrhosis receiving Sovaldi plus PEG/RBV demonstrated SVR12 rates of 86 per cent (30/35).

Genotype 2 patients also demonstrated high SVR12 rates across all treatment arms. SVR12 rates among patients receiving Sovaldi plus PEG/RBV were 94 per cent (15/16), and 100 per cent (17/17) and 87 per cent (13/15) for those receiving Sovaldi plus RBV for 24 and 16 weeks, respectively.

Sovaldi plus PEG/RBV and Sovaldi plus RBV were well tolerated. The most common adverse events in the study were fatigue, headache, insomnia and nausea. Overall, six patients (1 per cent) discontinued treatment due to adverse events, one of whom was treated with Sovaldi plus PEG/RBV.

"It remains difficult to achieve a virological response in genotype 3, which is one of the most prevalent genotypes in the world, with higher prevalence in Europe and Asia," said Graham R Foster, FRCP, PhD, professor of Hepatology, The Liver Unit, Queen Mary's University of London, Barts Health, London, United Kingdom.

"These results are compelling because they represent the highest cure rates observed among treatment-experienced, cirrhotic genotype 3 patients in any phase 3 clinical trial to date."

In a separate open-label phase 2 study of Harvoni conducted in France (Study GS-US-337-1119, O056), results demonstrated high SVR rates in both treatment-naïve and treatment-experienced patients with chronic HCV genotypes 4 or 5 infection, 50 percent of whom had cirrhosis.

Ninety-three per cent of patients with genotype 4 (41/44) and 95 per cent of patients with genotype 5 (39/41) achieved SVR12. Response rates were similar among both treatment-naïve and -experienced patients and regardless of cirrhosis.



The most common adverse events (affecting more than 10 per cent of patients) were asthenia, headache and fatigue. Most adverse events were mild or moderate in severity and none resulted in treatment discontinuation. There were no grade 3 or 4 clinical laboratory abnormalities.

"HCV genotype 4 and 5 are less prevalent than other genotypes and therefore, have traditionally not been closely studied," said Armand Abergel, MD, PhD, Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire-Estaing, Université d'Auvergne, Clermont-Ferrand, France.

"These data provide important evidence that the all-oral, ribavirin-free Harvoni regimen is both safe and effective for many patients with genotype 4 or 5, regardless of prior treatment experience."

The safety and efficacy of these investigational uses of Harvoni and Sovaldi have not been established.

Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment.

Amiodarone is not recommended for use with Sovaldi in combination with another Direct Acting Antiviral (DAA) due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease.

Amiodarone is not recommended for use with Harvoni due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease.

Rifampin and St. John's wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.

In addition to rifampin and St. John's wort, coadministration of Harvoni is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni.

Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.