Two phase III clinical trials evaluating the investigational use of once-daily tenofovir alafenamide (TAF, Gilead Sciences) 25 mg in treatment-naïve and treatment-experienced adults with HBeAg-negative and HBeAg-positive chronic hepatitis B virus (HBV) infection have met their primary objectives. The studies demonstrated that TAF was noninferior to tenofovir disoproxil fumarate (TDF, Viread, Gilead Sciences), based on the percentage of patients with HBV DNA levels below 29 IU/mL after 48 weeks of therapy. In addition, TAF demonstrated improved renal and bone laboratory safety parameters compared with TDF.
Studies 108 and 110 were randomized, double-blind, 96-week clinical trials involving a total of 1,298 treatment-naïve and treatment-experienced patients with chronic HBV. In study 108, 425 HBeAg-negative patients were randomly assigned to receive TAF (n = 285) or TDF (n = 140). In study 110, 873 HBeAg-positive patients were randomly assigned to receive TAF (n = 581) or TDF (n = 292).
The studies’ primary efficacy endpoint was the proportion of subjects with plasma HBV DNA levels below 29 IU/mL. Key secondary endpoints included the change from baseline in bone mineral density at the hip and spine at week 48, and the change from baseline in serum creatinine at week 48.
In study 108, 94% (268/285) of patients receiving TAF and 93% (130/140) of patients receiving TDF achieved HBV DNA levels below 29 IU/mL at week 48 (P = 0.47). In study 110, 64% (371/581) of TAF patients and 67% (195/292) of TDF patients achieved HBV DNA below 29 IU/mL at week 48 (P = 0.25).
Discontinuations due to adverse events were uncommon in both treatment arms (0.7% for both TAF and TDF) in Study 108, and in both treatment arms in study 110 (1.0% for both TAF and TDF). The most commonly reported adverse events in both studies included headache, upper respiratory tract infection, nasopharyngitis, and cough, and occurred at similar rates in patients receiving either TAF or TDF.
Changes in bone and renal laboratory parameters favored the TAF regimen. In both studies, patients receiving TAF experienced a significantly smaller mean percentage decrease from baseline in hip and spine bone mineral density at week 48 (P < 0.001) compared with patients receiving TDF. Smaller increases in serum creatinine were observed in patients receiving TAF in study 110 (P = 0.02). In addition, the median change in the estimated glomerular filtration rate (eGFR) from baseline to week 48 favored TAF in both studies (P < 0.01).
Based on the results from studies 108 and 110, Gilead plans to submit a regulatory application for TAF for chronic HBV infection during the first quarter of 2016.
TAF as a single agent for patients with chronic HBV infection is an investigational product, and its safety and efficacy have not been established.
Source: Gilead Sciences; January 5, 2016.