GILEAD ANNOUNCES NEW DATA FROM VIRAL HEPATITIS RESEARCH PROGRAMMES AT THE LIVER MEETING® 2019

-- Data Demonstrate Reductions in Hepatocellular Carcinoma in Hepatitis B (HBV) Patients Treated with Vemlidy®▼ (tenofovir alafenamide 25 mg, TAF) -- 

-- Improved Markers of Bone and Renal Safety Also Seen with TAF in Separate Analysis of HBV Patients with Hepatic or Renal Impairment -- 

-- Data on Investigational TLR8 Agonist GS-9688 Support Continued Advancement of the Company’s HBV Cure Research Programme -- 

BOSTON, November 8, 2019 – Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data on Vemlidy® (tenofovir alafenamide 25 mg, TAF) that continue to support an improved safety profile compared with tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (HBV) infection.1,2 These results, along with new data from Gilead’s HBV cure and hepatitis C (HCV) research programmes,3,4  are being presented at The Liver Meeting® 2019 in Boston this week.  

Chronic HBV infection is a leading risk factor for the development of hepatocellular carcinoma (HCC) globally.5 The impact of HBV treatment on HCC incidence was evaluated in a long-term analysis of two Phase 3 studies of TAF (Oral 0194), in which 1,632 HBV patients were randomised to receive either TAF or TDF once daily in two cohorts. Through three or five years of follow-up, dependent on cohort, HCC was observed in 21 patients (1.0 percent in the TAF group; 1.9 percent in the TDF group), with a median time to onset of 104 weeks. The HCC incidence observed in this study was significantly lower than the predicted incidence using the REACH-B model, particularly for patients without cirrhosis. Additional follow-up is needed to further characterise the impact of longer-term treatment on HCC risk reduction.6  

Tenofovir alafenamide is authorized in Europe for the treatment of chronic HBV infection in adults and adolescents (≥ 12 years with body weight of at least 35 kg).7 

“Chronic infection with hepatitis B virus can lead to an increased risk of developing serious and lifethreatening liver damage,” said Young-Suk Lim, M.D., Ph.D., lead study author and professor, Department of Gastroenterology, Liver Centre, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea. “This analysis suggests that sustained viral suppression from treatment with TAF may reduce the risk of hepatocellular carcinoma in chronic hepatitis B patients, which is the most common type of liver cancer in adults.” 

Markers of Bone and Renal Safety with TAF Data from multiple studies presented at The Liver Meeting® demonstrate continued viral suppression (HBV DNA <20 IU/mL) and improvements in bone and renal markers with TAF in patients with chronic HBV and also in high-risk HBV patients with hepatic or renal impairment.  

In an analysis from a Phase 3 study evaluating virally suppressed chronic HBV patients (Poster 0455), 243 patients who had previously been treated with TDF for a median of four years were switched to TAF for 48 weeks. Switching from TDF to TAF resulted in improvement in certain bone and renal markers regardless of the duration (<4 years vs ≥ 4 years) of prior TDF use.8 

In an open-label Phase 2 study (Poster 0483), 93 HBV patients with moderate to severe renal impairment or end-stage renal disease (ESRD) on chronic hemodialysis (HD) who were virally suppressed taking TDF and/or other antivirals for at least 48 weeks, were switched to TAF for 96 weeks.1 At week 24, all patients with ESRD and 97 percent of patients with moderate or severe renal impairment met the primary endpoint of maintaining viral load suppression. In renally-impaired HBV patients, switching to TAF from TDF resulted in increases in hip and spine bone mineral density and decreases in most bone turnover markers including in ESRD patients on HD, as well as decreases in renal tubular markers and increases in glomerular filtration rate (eGFRCG). Similar results were achieved in a Phase 2 open-label study of 31 virally suppressed HBV patients with moderate or severe hepatic impairment (Child-Turcotte-Pugh Class B or C) who were switched to TAF and treated for 24 weeks (Poster 0501).3 

HBV Functional Cure Research GS-9688 is an investigational oral selective small molecule agonist of toll-like receptor 8 (TLR8). In a Phase 2 multicentre, randomised, double-blind study of 48 virally suppressed chronic HBV patients (Poster 0697), GS-9688, taken in combination with oral antivirals, was well-tolerated over an extended dosing period and demonstrated dose-dependent pharmacodynamic activity.  Clinical activity was also evaluated; five percent of patients receiving GS-9688 achieved a ≥ 1 log10 IU/mL decline in hepatitis B surface antigen (HBsAg) levels or hepatitis B e-antigen (HBeAg) loss at 24 weeks. These data support ongoing studies of GS-9688 as well as novel combinations aimed at achieving a functional cure of HBV.3 

The safety and efficacy of GS-9688 have not been established. GS-9688 is an investigational compound and is not approved by the U.S. Food & Drug Administration (FDA), European Medicines Agency (EMA) or any other regulatory authority.  

HCV Treatment in Paediatric Patients  There are limited approved HCV treatment options for children younger than 12 years old, particularly those with HCV genotypes 2 and 3. In an open-label study of patients 6 to <18 years of age with HCV genotypes 1, 2, 3, 4 and 6 (Poster 0748), 12 weeks of treatment with Epclusa®▼ (sofosbuvir/velpatasvir) resulted in a cure rate (SVR12) of 95 percent (97/102) in patients 12 to <18 years old and 92 percent (67/73) in those 6 to <12 years old. Most Adverse Events (AEs) were mild or moderate in severity; four patients experienced a serious AE, one which was attributed to treatment. The most common AEs (>15 percent of patients) were headache, fatigue and nausea in adolescents, and vomiting, cough and headache in patients 6 to <12 years old. The study is ongoing in children ages 3 to <6 years old.4 

The use of sofosbuvir/velpatasvir in the aforementioned patient population is investigational; its safety and efficacy have not been established. Sofosbuvir/velpatasvir is indicated in Europe for the treatment of adults with chronic HCV genotype 1-6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for adult patients with decompensated cirrhosis. Addition of ribavirin may be considered in those with GT3 infection and compensated cirrhosis*. The European Summary of Product Characteristics for sofosbuvir/velpatasvir includes a special warning and precaution for use regarding the risk of HBV reactivation in HBV/HCV co-infected patients. 9   

About Gilead Sciences 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. 

 References  

1 Janssen H, et al. Efficacy and Safety of Switching to Tenofovir Alafenamide (TAF) in Virally Suppressed Chronic Hepatitis B (CHB) Patients with Renal Impairment: Week 24 Results from a Phase 2 Open-Label Study. AASLD The Liver Meeting™; 2019 November 08-12; Boston United States of America. Poster 0483 2 Lim YS, et al. Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) in Virally Suppressed Chronic Hepatitis B (CHB) Patients with Hepatic Impairment: Week 24 Results from a Phase 2 Open-Label Study. AASLD The Liver Meeting™; 2019 November 08-12; Boston United States of America. Poster 0501 3 Gane E, et al. Efficacy and Safety of Oral TLR8 Agonist GS-9688 in Virally-Suppressed Adult Patients with Chronic Hepatitis B: A Phase 2, Randomized, Double-Blind Placebo-Controlled, Multi-Center Study. AASLD The Liver Meeting™; 2019 November 08-12; Boston United States of America. Poster 0697 4 Jonas M, et al. The Safety and Efficacy of Sofosbuvir/Velpatasvir in Pediatric Patients 6 to < 18 years old with Chronic Hepatitis C Infection. AASLD The Liver Meeting™; 2019 November 08-12; Boston United States of America. Poster 0748 5 Petruzziello A. Epidemiology of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Related Hepatocellular Carcinoma. Open Virol J. 2018; 12: 26–32. Published online 2018 Feb 28. doi: 10.2174/1874357901812010026 Available at:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842386/ [Last accessed November 2019] 6 Lim YS, et al. Impact of Treatment With Tenofovir Alafenamide (TAF) or Tenofovir Disoproxil Fumarate (TDF) on Hepatocellular Carcinoma (HCC) Incidence in Patients with Chronic Hepatitis B (CHB). AASLD The Liver Meeting™; 2019 November 08-12; Boston United States of America. Oral 0194.  7 Medicines. EMA. Product. Vemlidy. [Online] Available at: https://www.ema.europa.eu/en/documents/productinformation/vemlidy-epar-product-information_en.pdf [Last accessed November 2019]  8 Chan H, et al. Impact of Prior Tenofovir Disoproxil Fumarate (TDF) Treatment Duration on Tenofovir Alafenamide (TAF) Safety Profile in Virally Suppressed Chronic HBV Patients Switched from TDF to TAF. AASLD The Liver Meeting™; 2019 November 08-12; Boston United States of America. Poster 0455 9 Medicines. EMA. Product. Epclusa. [Online] Available at: https://www.ema.europa.eu/en/documents/productinformation/epclusa-epar-product-information_en.pdf [Last accessed November 2019]