Assembly Biosciences' investigational drug, ABI-5366, is showing promise as a novel treatment for recurrent genital herpes. Interim results from the Phase 1a study indicate a favorable safety profile and a long half-life, supporting less frequent oral dosing. The company has initiated Phase 1b trials to further evaluate the drug's potential in individuals with recurrent genital herpes.
Phase 1a Results: Safety and Pharmacokinetics
The Phase 1a/b study is a randomized, blinded, and placebo-controlled trial. The Phase 1a portion focused on assessing the safety, tolerability, and pharmacokinetics (PK) of ABI-5366 in healthy participants. Single ascending doses of 10 mg, 30 mg, 100 mg, and 350 mg were evaluated. The extended follow-up period, initially 70 days, was increased to 100 days due to the drug's extended PK profile.
ABI-5366 demonstrated a mean half-life of approximately 20 days when administered orally. This supports the feasibility of both once-weekly and potentially once-monthly oral dosing regimens. The drug was well-tolerated across all tested doses, with treatment-emergent adverse events (AEs) being mild to moderate in intensity and not related to the study treatment. There were no serious AEs, treatment-related grade 3 or 4 laboratory abnormalities, or clinically significant ECG abnormalities.
Phase 1b: Evaluating Efficacy in Recurrent Genital Herpes
Building on the Phase 1a results, Assembly Bio has commenced screening for the Phase 1b portion of the study. This phase will involve participants seropositive for HSV-2 with recurrent genital herpes. Multiple ascending doses of ABI-5366 will be evaluated under both weekly and monthly oral regimens over a 29-day treatment interval. Participants will be randomized 20:5 between ABI-5366 and placebo in each cohort.
In addition to safety, tolerability, and PK assessments, Phase 1b will also evaluate antiviral activity. Key measures include changes in viral parameters such as HSV-2 shedding rate and virus levels from genital swab samples. Clinical parameters, including lesion recurrence rate and duration, will also be monitored. The data from this trial will inform dose selection for a future Phase 2 trial. Interim data from Phase 1b is expected in the first half of 2025.
The Need for New Therapies
Recurrent genital herpes, caused by herpes simplex virus (HSV), affects millions globally, leading to painful lesions and significant psychological and social distress. Current treatments, primarily nucleoside analogs, are only partially effective in preventing recurrences and reducing transmission. As Dr. Anna Wald from the University of Washington School of Medicine notes, "The need for new, innovative chronic suppressive therapies is urgent."
ABI-5366, a helicase-primase inhibitor, targets a viral enzyme complex essential for HSV replication. This mechanism has shown potential for superior efficacy compared to nucleoside analogs. Assembly Bio's CEO, Jason Okazaki, stated, "The current standard of care for suppressive therapy often falls short in preventing recurrences, and no new therapies have been approved in decades. With the exceptional oral half-life of ABI-5366, we look forward to exploring its potential for both once-weekly and once-monthly oral dosing."
