Drug name
Last update: Sep 2025VH-280 (VH-4004280)
Developer(s)
Drug information
Not provided
Not provided
investigational - investigation was discontinued by ViiV
Small molecule
Capsid inhibitor
VH4004280 (also known as VH-280 or GSK4004280) is an investigational oral HIV-1 capsid inhibitor. This novel antiretroviral targets the HIV-1 capsid protein, a crucial component involved in multiple stages of the viral lifecycle. VH-280 functions by binding to a pocket formed between adjacent capsid proteins within the mature capsid hexamer. This interaction disrupts essential viral processes. Preclinical studies have demonstrated that VH-280 exhibits potent antiviral activity, with half-maximal effective concentrations (EC50 values) in the picomolar range against a broad spectrum of HIV-1 laboratory strains and clinical isolates. Its mechanism is understood to be multi-stage, impacting both early and late phases of the HIV-1 life cycle.
investigational
investigational
Therapeutic area(s)
- HIV
- Pre-Exposure Prophylaxis (PrEP)
- Treatment
- Prevention
Administration route
Oral, Subcutaneous, Intramuscular, To be determined
Associated long-acting platforms
Oral solid form
Use of drug
- Self-administered
- Other/Variable/Unknown : to be determined
Not provided
Dosage
to be determined
to be determined
to be determined
Not provided
Not provided
Associated technologies
Not provided
Comment & Information
Developer(s)
ViiV Healthcare
Drug structure
Scale-up and manufacturing prospects
Detailed manufacturing information is not currently available for this compound.
Detailed manufacturing information is not currently available for this compound.
Detailed manufacturing information is not currently available for this compound.
Detailed manufacturing information is not currently available for this compound.
Excipients
Not provided
Not provided
Not provided
Delivery device(s)
Not provided
There are either no relevant patents or these were not yet submitted to LAPaL
Publications
Thakkar N, Griesel R, Pierce A, et al. Clinical Pharmacokinetics and Safety of a New HIV-1 Capsid Inhibitor, VH4004280, After Oral Administration in Adults Without HIV. Infect Dis Ther. Published online April 26, 2025. doi:10.1007/s40121-025-01154-x
Introduction: The pharmacokinetics, drug-drug interaction potential, and safety of a new HIV-1 capsid inhibitor, VH4004280 (VH-280), are described in this first-time-in-human study.
Methods: This randomized, double-blind, placebo-controlled, phase 1 study assessed oral VH-280 in adults without HIV. In parts 1 and 3, VH-280 was administered as powder-in-bottle (PiB) and tablet formulations, respectively, in single ascending doses. In part 2, VH-280 was administered as a PiB formulation once daily for 14 days in multiple ascending doses. In addition, in part 2, the effect of VH-280 on cytochrome P450 3A (CYP3A) activity was evaluated using midazolam as a probe substrate.
Results: In total, 73 participants were included (VH-280, n = 57; placebo, n = 16). Plasma exposures for VH-280 were broadly dose-proportional, and median time to maximum observed concentration was 9.0-17.0 h for the PiB and tablet formulations. Geometric mean terminal half-life was 145.8-207.8 h (> 6 days). Compared with PiB, exposures for the tablet formulation were 45-56% lower. Concomitant administration of midazolam after single and multiple doses of VH-280 did not result in clinically significant changes in midazolam or 1-hydroxymidazolam exposures; therefore, VH-280 is not anticipated to inhibit or induce CYP3A4. VH-280 was well-tolerated. Frequency of adverse events (AEs) was comparable between placebo and VH-280 groups. Adverse events related to VH-280 were primarily grade 1. There were no serious AEs, AEs leading to withdrawal from drug or study, or deaths. No trends in vital signs, electrocardiograms, or laboratory hematology parameters were observed, and there were no clinically relevant changes in chemistry parameters.
Conclusions: Data from this first-time-in-human study further characterize the pharmacokinetics of VH-280 after oral administration, providing support for the development of new capsid inhibitors as part of a complete long-acting regimen for the treatment and prevention of HIV-1.
Clinical trial registration: ClinicalTrials.gov, NCT05163522.
Additional documents
No documents were uploaded
Collaborate for development
Consider on a case by case basis, collaborating on developing long acting products with potential significant public health impact, especially for low- and middle-income countries (LMICs), utilising the referred to long-acting technology
Share technical information for match-making assessment
Provide necessary technical information to a potential partner, under confidentiality agreement, to enable preliminary assessment of whether specific medicines of public health importance in LMICs might be compatible with the referred to long-acting technology to achieve a public health benefit
Work with MPP to expand access in LMICs
In the event that a product using the referred to long-acting technology is successfully developed, the technology IP holder(s) will work with the Medicines Patent Pool towards putting in place the most appropriate strategy for timely and affordable access in low and middle-income countries, including through licensing