Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from several Phase 2 and Phase 3 studies evaluating investigational uses of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) for the treatment of chronic hepatitis C virus (HCV) infection in patients with limited or no treatment options, including patients with decompensated cirrhosis, patients with HCV recurrence following a liver transplant and patients who failed previous treatment with other direct acting antivirals.
These data will be presented this week at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2014) in Boston.
“Chronic hepatitis C patients with advanced liver disease are among the most difficult to cure and traditionally have had limited or no treatment options,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. “The data presented this week demonstrate that Harvoni provides high cure rates for patients with advanced liver disease, as well as for those who failed prior treatment with other antivirals, including sofosbuvir-based regimens.”
Harvoni was approved by the U.S. Food and Drug Administration and Health Canada in October 2014 and is the first once-daily single tablet regimen for the treatment of chronic HCV genotype 1 infection in adults. Applications are pending in the European Union, Japan and New Zealand.
Advanced Liver Disease
In a pooled analysis of Phase 2 and Phase 3 open-label studies (Oral #82) in more than 500 genotype 1 HCV infected patients with compensated cirrhosis who received Harvoni alone or with ribavirin (RBV) for 12 or 24 weeks, 96 percent of patients achieved sustained virologic response (SVR12). Patients who achieve SVR12 are considered cured of HCV infection.
Two prospective analyses from a Phase 2 open-label study (Study GS-US-337-0123) evaluating patients with decompensated cirrhosis and those with HCV recurrence following liver transplantation also are being presented. In the first subgroup (Oral #239), 108 genotype 1 and 4 infected patients with decompensated cirrhosis, including those with moderate hepatic impairment (Child-Pugh-Turcotte (CPT) Class B) and severe hepatic impairment (CPT Class C), received Harvoni plus RBV for 12 or 24 weeks. Overall, SVR12 rates were 87 percent (n=45/52) in the 12-week arm and 89 percent (n=42/47) in the 24-week arm.
The second subgroup (Oral #8) evaluated 12 or 24 weeks of Harvoni plus RBV among 223 genotype 1 and 4 patients who developed HCV recurrence following liver transplantation. Among non-cirrhotic patients, SVR12 rates were 96 percent (n=53/55) and 98 percent (n=55/56) following 12 and 24 weeks of treatment, respectively. For patients with compensated cirrhosis, SVR12 rates were 96 percent for both 12 weeks (n=25/26) and 24 weeks (n=24/25) of therapy. SVR12 rates among patients with decompensated cirrhosis were 81 percent for both 12 weeks (n=25/31) and 24 weeks (n=17/21) of therapy.
Retreatment of Patients Who Failed Prior Therapy
Study GS-US-337-0121 (Late Breaker Oral #LB-6) evaluated 155 genotype 1 patients with compensated cirrhosis who had failed prior treatment with pegylated interferon (PegIFN)/RBV and subsequently PegIFN/RBV plus a protease inhibitor. In this study, patients were randomized (1:1) to receive Harvoni plus RBV for 12 weeks or Harvoni alone for 24 weeks. Ninety-six percent (n=74/77) of those receiving Harvoni plus RBV for 12 weeks and 97 percent (n=75/77) of those receiving Harvoni for 24 weeks achieved SVR12.
In a second study (Oral #235), 51 genotype 1 patients who previously failed SOF/PegIFN/RBV, SOF/RBV or a SOF placebo/PegIFN/RBV treatment regimen received Harvoni plus RBV for 12 weeks. Twenty-nine percent of study patients (n=15/51) had cirrhosis. Ninety-eight percent (n=50/51) achieved SVR12 following 12 weeks of treatment with Harvoni plus RBV.
In all of these studies, Harvoni was well tolerated and its safety profile was generally consistent with that observed in clinical trials of Harvoni. Adverse events included fatigue, headache, nausea and anemia, which was more common among patients taking RBV. Grade 3/4 laboratory abnormalities were infrequent and included decreases in hemoglobin, which is consistent with RBV-associated anemia.
The safety and efficacy of Harvoni have not been established for the investigational uses described above.
Important Safety Information About Harvoni
Warnings and Precautions
Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi).
Most common (≥10 percent, all grades) adverse reactions were fatigue and headache.
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.
Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.