Of those, 115 LdT and 117 TDF patients were included in the mITT population. Baseline characteristics were well matched between the treatment groups. The primary efficacy endpoint for non-inferiority was met, with 92.1% LdT and 95% TDF patients achieving HBV DNA level <300 copies/ mL at Week 52 (Table). There were
no deaths. Serious adverse events (SAEs), reported in 17 patients (8 in Akt inhibitor LdT and 9 in TDF), were not related to the treatment according to investigator’s opinion. Twice as many patients from the LdT monotherapy arm with an abnormal estimated glomerular filtration rate (eGFR) at baseline reverted to normal eGFR compared to the TDF mono-therapy arm. Conclusions: LdT is effective and non-inferior to TDF for the treatment of HBeAg-negative CHB. LdT was associated with an improvement in renal function (eGFR) when compared to TDF. Table. Efficacy and safety outcomes
Disclosures: Zahary Krastev – Grant/Research Support: Gilead Sciences INC, Gilead DNA Methyltransferas inhibitor Sciences INC, Gilead Sciences INC, Gilead Sciences INC, novartis David Mc Neeley – Employment: Novartis Pharmaceutical Corporation; Stock Shareholder: Novartis Pharmaceutical Corporation Kamal A. Hamed – Employment: Novartis; Stock Shareholder: Novartis The following people have nothing to disclose: Iskren A. Kotzev, Mustafa K. Celen Background & Aims: GS-9620, an oral agonist of toll-like receptor 7 (TLR7), is in phase 2 trials for the treatment of chronic hepatitis B (CHB). Infrequent dosing of GS-9620 (e.g. once a week) induced prolonged suppression of serum viral DNA and antigens in animal models of CHB. Here we investigated the molecular mechanisms that contribute to the antiviral response to GS-9620 by evaluating the antiviral activity of TLR7 agonists in vitro. Methods: Primary human hepatocytes (PHH) were infected with
HBV and ≥3 days later were treated with a TLR7 agonist (compound A), with media from human PBMCs treated with the TLR7 agonist (TLR7 check conditioned media; TLR7-CM) or with recombinant cytokines. Antiviral activity was evaluated by quantifying extracellular HBV DNA (qPCR), HBeAg and HBsAg (ELISA), as well as intracellular HBV RNA (qRT-PCR). Results: The TLR7 agonist compound A (a close analog of GS-9620), had no direct antiviral activity in HBV-infected PHH, consistent with the lack of functional TLR7 in hepatocytes. In contrast, sustained exposure of HBV-infected PHH to TLR7-CM strongly reduced the levels of HBV DNA and HBeAg (>90%), as well as HBsAg and HBV RNA (>75%), without detectable toxicity. Reductions in viral parameters were observed when PHH were treated with TLR7-CM early (3 days) or late (13 days) post-infection, but were not induced by media from control DMSO-treated PBMCs. We next compared the durability of short (3 day) and long (10 day) treatment of HBV-infected PHH with TLR7-CM. Short duration treatment (days 3-6 post-infection) only transiently reduced HBeAg.