13 November 2018 - - US-based biopharmaceutical company Gilead Sciences, Inc. (NASDAQ: GILD) has presented results from studies investigating Epclusa (sofosbuvir 400mg/velpatasvir 100mg) in chronic hepatitis C virus infected patients with severe renal impairment undergoing dialysis and Harvoni (ledipasvir/sofosbuvir) in pediatric HCV patients aged three to five years, adding to the efficacy and safety profile of sofosbuvir-based regimens across diverse patient populations, the company said.

These results, along with data from Gilead's hepatitis B virus cure development program, are being presented at The Liver Meeting 2018 in San Francisco this week.

Results from an open-label Phase 2 study demonstrated that treatment with the once-daily single-tablet regimen of Epclusa for 12 weeks in patients with genotype 1, 2, 3, 4 or 6 HCV and severe renal impairment undergoing dialysis resulted in cure rates (SVR12, or undetectable viral load 12 weeks after completion of therapy) of 95 % (n=56/59) with only two patients experiencing virologic failure.

The most common adverse events (>10 %) were headache, fatigue, nausea, vomiting and insomnia. No patients discontinued therapy due to an adverse event.

In another open-label Phase 2 study, children aged three to five years old with genotype 1 or 4 HCV infection received weight-based oral dosing of ledipasvir/sofosbuvir granules 33.75 mg/150 mg if < 17 kg or 45 mg/ 200 mg if ≥ 17 kg) once-daily for 12 weeks.

Overall, 97 % (n=33/34) of the patients were cured, and none experienced virologic failure. The most common AEs (>10 %) were vomiting, cough, pyrexia, rhinorrhea and streptococcal pharyngitis.

One patient discontinued treatment due to an adverse event of abnormal drug taste.

The use of Epclusa and Harvoni, including granules formulation, in the aforementioned patient populations is investigational; their safety and efficacy have not been established.

The granule formulation is not approved. Epclusa and Harvoni are both indicated in the US for the treatment of chronic HCV infection in patients with no cirrhosis or compensated cirrhosis: Epclusa for adults with genotypes 1-6; and Harvoni for patients 12 years and older (or ≥35 kg) with genotypes 1, 4, 5 and 6.

The US product labels for Epclusa and Harvoni each contain a Boxed Warning for the risk of hepatitis B reactivation in HCV/HBV co-infected patients. See below for US Important Safety Information.

Gilead is presenting data on GS-9688, an investigational, oral selective toll-like receptor 8 agonist, one of several compounds under investigation as part of Gilead's HBV cure programme. The data support continued development of GS-9688 as a potential therapeutic approach for achieving a functional cure for patients with chronic HBV infection.

In the first-in-human, healthy volunteer safety study, GS-9688 was well-tolerated at single ascending doses up to 5mg and resulted in pharmacodynamic activity as demonstrated by the production of the systemic cytokines IL-1RA and IL-12p40 and by the activation of key relevant immune cells including natural killer cells and mucosal-associated invariant T cells.

The most commonly reported AEs among people receiving doses up to and including 5 mg were nausea and vomiting. There were no reports of Grade 3 or higher AEs, laboratory AEs or serious adverse events and no discontinuations or deaths.

In a Phase 1b safety and tolerability study of GS-9688 in HBV chronically infected patients, dose-dependent activation of the cytokines IL-12p40 and IL-1RA was demonstrated with once weekly dosing for up to 4 weeks in viremic and virally-suppressed patients.

There were no reports of SAEs; the most common AEs were headache and nausea. Based on these data, GS-9688 is currently being evaluated in Phase 2 studies in patients with chronic hepatitis B.

GS-9688 is an investigational agent and not approved; its safety and efficacy have not been established.

Presentations on Vemlidy (tenofovir alafenamide 25mg, TAF) add further evidence to its established safety and efficacy profile in adults with chronic HBV and compensated liver disease, including longer term data on the safety of Vemlidy in virologically suppressed HBV patients.

Through three years of treatment, patients originally randomized to receive TAF continued to show an improved bone and renal safety profile compared to treatment with tenofovir disoproxil fumarate 300mg with maintained viral suppression.

In a separate study in post-liver transplant patients virally suppressed on TDF-based regimens, switching to TAF maintained viral suppression in all TAF-treated patients with improvements in renal function and bone mineral density, after 48 weeks of treatment.

The use of Vemlidy in post-liver transplant patients is investigational; its safety and efficacy have not been established.

Vemlidy is indicated in the US for the treatment of chronic HBV infection in adults with compensated liver disease.

The US Prescribing Information for VEMLIDY contains a Boxed Warning regarding the risk of post treatment severe acute exacerbation of hepatitis B; see below for Important Safety Information.

Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need.

The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.