ST Pharm has achieved a significant milestone in HIV drug development with pirmitegravir, the first allosteric integrase inhibitor (ALLINI) to demonstrate clinical proof of concept in adults with HIV-1 infection. Results presented at IDWeek 2025 showed the investigational drug achieved substantial viral load reductions while maintaining a favorable safety profile, potentially validating an entirely new mechanism for HIV treatment.
Novel Mechanism Targets Viral Assembly
Pirmitegravir represents a breakthrough in HIV therapeutics as the first ALLINI to reach clinical validation. Unlike conventional integrase strand transfer inhibitors such as dolutegravir and bictegravir, pirmitegravir targets noncatalytic sites of the HIV-1 integrase enzyme through allosteric inhibition. The drug binds to the lens epithelium-derived growth factor/p75 allosteric site on the HIV-1 integrase enzyme, disrupting normal multimerisation and mislocalising viral ribonucleic acid.
This unique mechanism prevents proper viral assembly and results in the production of noninfectious viral particles, offering potential advantages in resistance management compared to existing therapies. The approach validates allosteric inhibition of integrase as clinically viable, marking the potential emergence of the first new HIV mechanism in more than a decade.
Strong Efficacy Results in Phase IIa Trial
The ongoing Phase IIa randomised, double-blind, placebo-controlled trial is evaluating pirmitegravir's antiviral efficacy, safety, and pharmacokinetics in antiretroviral therapy-naive adults with HIV-1 infection. Interim results presented by Xue Meng from ST Pharm at IDWeek 2025 demonstrated significant viral load reductions after ten days of once-daily oral treatment.
Participants receiving 200mg pirmitegravir showed viral load reductions of -1.55 log₁₀ copies/ml, while the 400mg dose group achieved -1.19 log₁₀ copies/ml reductions, compared to -0.25 log₁₀ copies/ml for placebo. Both treatment groups exceeded the U.S. FDA's primary efficacy threshold of 0.5 log₁₀ for HIV-1 infection treatments, with the average decrease ranging from 1.191 to 1.552 log₁₀ copies.
Favorable Safety and Pharmacokinetic Profile
The drug demonstrated excellent tolerability across both dose levels tested. Among 16 adverse events reported in the interim analysis, only three were considered possibly related to the study drug. Treatment was well tolerated with mild gastrointestinal adverse events such as nausea and diarrhea, and no serious events or treatment discontinuations were observed.
Pharmacokinetic findings support the once-daily dosing regimen, with rapid absorption occurring within one hour and peak plasma concentrations reached approximately 4.5 to 5.5 hours after administration. The drug showed a half-life of 12-14 hours (ranging from 11.6 to 13.7 hours) with minimal accumulation after repeated dosing, and exposure increased in a dose-dependent but less-than-dose proportional manner.
Clinical Development Progress
ST Pharm is currently enrolling participants for Cohort 3 at 600mg doses, with plans to receive the final clinical study report in the first half of 2026. Earlier Phase I studies in healthy volunteers established favorable tolerability and predictable pharmacokinetics, supporting the current dose-ranging approach.
The drug has garnered significant attention in the pharmaceutical industry, being highlighted as one of the "HIV clinical trials to watch in 2024" by Clinical Trials Arena, reflecting high global expectations for this first-in-class candidate.
Market Implications
If efficacy and safety are sustained in the ongoing 600mg cohort and later-phase studies, pirmitegravir could represent a significant advancement in HIV therapeutics. While the HIV therapeutics market is large and highly competitive with a range of established drug classes, there remains a continued need for investment in therapeutics with novel mechanisms of action to combat drug resistance.
The successful clinical validation of allosteric integrase inhibition signals renewed momentum in next-generation HIV therapeutics and could provide a valuable complement to current antiretroviral therapy regimens.
