BOSTON, MA—Once-daily-administered combination of the investigative direct-acting antivirals AL-335 and odalasvir (ODV), and simeprevir (SMV) is well tolerated in healthy volunteers, and is now under study among patients with hepatitis C virus (HCV), according to findings from an open-label Phase 1 study presented at The Liver Meeting® 2016.

“AL-335, ODV, and SMV administered as monotherapies or in combination were safe and well tolerated,” reported Thomas Kakuda, PharmD, Alios BioPharma, South San Francisco, CA.

No serious adverse events (SAEs) were reported. Twenty-one treatment emergent adverse events (TEAEs) occurred in 12 patients (37.5%); all were “non-serious, mild or moderate in intensity, with no safety signals identified,” Dr. Kakuda said. “No clinically significant changes in laboratories, vital signs, physical exams or ECGs were identified.” The most frequently reported TEAE was fatigue (8 events).

The research team sought to evaluate how ODV and SMV at different doses affect AL-335 prodrug, a monophosphate precursor (ALS-022399), and a parent nucleoside (ALS-022227) pharmacokinetics in health volunteers. Secondary goals of the study included evaluation of safety and efficacy of oral AL-335 alone or in combination with different doses of ODV and/or SMV in healthy volunteers.

AL-335 is an investigational uridine nucleotide analog prodrug. The investigational P-gp inhibitor odalasvir (ODV) has demonstrated “potent activity” against HCV NS5B. And SMV is an approved NS3/4 HCV protease inhibitor.

Alone or in combination, ODV and SMV had a significant effect on AL-335/metabolites, Dr. Kakuda reported. SMV had “no apparent effect” on the pharmacokinetics of parent nucleoside (ALS-022227), whereas ODV increased ALS-022227.

“AL-335 had no effect on ODV or SMV pharmacokinetics,” he said. “ODV and SMV when administered independently or in combination, increased AL-335 and ALS-022399 exposures but only ODV increased ALS-022227 exposure.”

ODV and SMV also increased exposure of one-another, he said.

A Phase 2a trial of AL-335 plus ODV with or without SMV is underway to assess safety, efficacy, and pharmacokinetics in hepatitis C virus (HCV)-infected patients.