You are here
Early Evidence of Antiviral Activity&Safety of ABX464 in HIV Treatment-Naïve Patients
Didier Scherrer1;Jean-Marc Steens2; Supparatpinyo Kuanchai3; Ratanasuwan Winai4; Kiat Ruxrungtham5; Regine Rouzier6; Jamal Tazi7; Paul Gineste2; Hartmut Ehrlich2; Robert Murphy8
1ABIVAX, Montpellier, France;2ABIVAX, Paris, France;3Rsr Inst for Hlth Sciences, Chiang Mai Univ, Chiang Mai, Thailand;4Siriraj Hosp, Bangkok, Thailand;5HIV-NAT, Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand;6Cap Rsr, Phoenix, Mauritius;7Univ of Montpellier, Montpellier, France;8Northwestern Univ, Feinberg Sch of Med, Chicago, IL, USA
ABX464 is a first-in-class antiviral drug candidate for the treatment of patients with HIV-infection. It is an orally available small molecule that blocks HIV replication through an entirely novel mechanism, inhibition of Rev activity. Preclinical data in humanized mice showed that ABX 464 monotherapy had an antiviral effect which was sustained after treatment interruption ( Campos et al, Retrovirology 2015 12:30 )
A prior food-effect study demonstrated a 3-fold increase in parent drug exposure when administered with food without a significant impact on the active glucuronide metabolite.
The objective of this study was to evaluate the safety of ABX-464 at ascending doses versus placebo in HIV-infected treatment-naive patients. Patients were randomized into successive cohorts of 8 patients where 6 received 14-or 21 days of ABX 464 and 2 placebo.
Patients from Mauritius and Thailand were included in the study after confirmation of HIV infection and no history of prior antiretroviral therapy.
At day 0, patients received the first dose of ABX-464/ placebo in a once daily schedule. Safety assessments and laboratory parameters were recorded throughout the study.
After completion of each cohort, a DSMB reviewed safety data and recommended whether the next cohort be initiated at a higher dose. Successive cohorts received 25, 50, 75, 100 and 150 mg QD. The 25, 50 and 100 mg.cohorts took drug fasting for 21 days, the 75 and 150 mg cohorts took drug with food for 14 days.
Safety and Tolerability : The main adverse events noted were nausea, vomiting and headache. All adverse events were grade 1 or 2 and all patients completed at least 14 days of treatment.
Viral load reduction > 0.5 log was observed in 1/6 patients in the 75 mg cohort, 2/6 patients in the 100 mg cohort and 4/6 patients in the 150 mg cohort; there were no significant viral load changes in the 6 placebo patients from these cohorts.
ABX 464 was well tolerated in this first study in HIV infected patients.
ABX 464 monotherapy showed early antiviral activity in HIV-infected treatment naïve patients. These results warrant the further planned development of this novel acting antiretroviral drug.