GS-5366

GS-5366, formerly ABI-5366, is an experimental long-acting oral antiviral for recurrent genital HSV-2. It is a separate candidate from GS-1179, which has its own trial and evidence record.

A sponsor-funded Phase 1b presentation reported much less HSV-2 shedding and lower genital-lesion rates with selected GS-5366 regimens than with placebo. The 29-day analysis was small and based on an interim data cutoff; it does not establish lasting benefit, transmission prevention, long-term safety, or a clinically validated monthly regimen.

HSVHQ lists the program as Discontinued because the latest checked filing says Gilead does not intend to develop GS-5366 further "at this time." That wording does not establish scientific failure or permanent abandonment.

GS-5366 blocks the HSV helicase-primase complex, part of the machinery the virus uses to copy its DNA. Company sources describe laboratory activity against HSV-1 and HSV-2, but the human antiviral study evaluated adults with recurrent genital HSV-2.

Assembly Biosciences discovered the candidate and initially developed it as ABI-5366. Gilead exercised its license option in December 2025, renamed it GS-5366, and assumed control of further clinical development after transition activities.

The first human study tested single ascending doses in healthy adults and multiple-dose regimens in adults with recurrent genital HSV-2. It examined safety, drug exposure, HSV-2 shedding from twice-daily anogenital swabs, and genital-lesion outcomes.

NCT06385327 began in May 2024, enrolled 115 people across its Phase 1a and Phase 1b parts, and completed in February 2026. ClinicalTrials.gov had no posted results through September 4, 2026.

The detailed public antiviral analysis uses a November 25, 2025 interim cutoff and covers 76 Phase 1b participants: 15 pooled placebo recipients, 20 assigned to a 150 mg loading dose followed by 30 mg weekly, 20 assigned to 350 mg weekly, and 21 assigned to a 350 mg loading-dose alternative. One person in the last group was excluded from the efficacy analysis.

Symptoms and anogenital or lesion swabs were collected twice daily during a 29-day evaluation. Participants had completed at least through day 53 at the interim cutoff, not necessarily the full follow-up shown in the study design.

HSV-2 was detected on 0.9% of assessed swabs in the 350 mg weekly group and 14.9% in the pooled placebo group. Overall genital-lesion rates were 1.1% and 18.3%, respectively, while lesions with HSV-2 detected were reported on 0.5% and 16.2% of assessed days.

The presentation reported corresponding relative reductions of 94%, 94%, and 97%, with nominal statistical significance. These short-window comparisons are antiviral and lesion signals; they are not direct evidence about transmission or long-term recurrence control.

In the loading-dose alternative group, shedding, overall-lesion, and HSV-2-confirmed-lesion rates were 3.5%, 6.5%, and 2.0%. Participants received five 350 mg loading doses over seven days and then no additional dose during the 29-day evaluation, so this was a simulated one-month interval rather than repeated monthly treatment.

The lower weekly regimen had a 14.5% shedding rate versus 14.9% with placebo, and the presentation described no apparent antiviral effect at that regimen. Findings from the two regimens showing an antiviral signal should not be generalized to every dose tested.

Treatment-emergent adverse events were common across all groups, including placebo. The presentation reported no grade 3 or 4 treatment-emergent adverse events and no treatment-emergent serious adverse events, but it also recorded some grade 3 laboratory abnormalities; a small, short study cannot establish long-term or uncommon safety outcomes.

The most defensible evidence-maturity label is early human evidence. Selected regimens produced controlled short-window evidence that GS-5366 affected genital HSV-2 shedding and lesions, while the lower weekly regimen did not show an apparent antiviral effect.

The study did not establish durable symptom or recurrence benefit, prevention of transmission, comparative superiority over GS-1179 or existing antivirals, or effectiveness with repeated long-term monthly dosing.

GS-5366 is intended to suppress viral replication. The checked evidence does not show that it removes latent HSV or cures the infection.

Gilead controls further development after exercising its option for GS-5366 in December 2025. The latest checked filing says Gilead does not intend to develop the candidate further "at this time," which supports HSVHQ's current Discontinued label but not a Failed label or a claim of permanent abandonment.

GS-1179 is the separate helicase-primase inhibitor Gilead selected to advance. GS-1179 results cannot be attributed to GS-5366, and the selection decision does not by itself show that one candidate is clinically superior.

No next development milestone for GS-5366 was established in the checked record. The page should be revisited if Gilead changes the program's status, a later trial is registered, registry results are posted, a full clinical report appears, or the selection rationale is disclosed.