VH4524184 / ViiV Healthcare, GSK, Shionogi - LARVOL DELTA

The Evolution of Integrase Strand Transfer Inhibitors: VH-184, a 3rd-Generation Inhibitor with an Enhanced Resistance Profile (IDWeek 2026) - No abstract available

Human Immunodeficiency Virus • Infectious Disease

Improving transparency on patenting strategies of HIV medicines candidates to anticipate access challenges (AIDS 2026) - " Based on monitoring of clinical trials for new HIV antiretrovirals (ARVs), the following compounds were selected: GS-1614; GS-6212; GS-5894; GS-4182; GS-1720, VH4011499; VH4004280; VH4367310; VH-310; VH4524184; MK-8527; MK-850, islatravir... The findings have shown the multiple patenting on key antiretrovirals – reflecting the evergreening strategy - and an initial patent filing for newer compounds, allowing national-level monitoring by MMA members, and anticipating patent applications to be challenged. However, the lack of transparency of chemical structures has hindered the ability to develop an accurate patent landscape, which is an access challenges to promising candidates in the drug pipeline."

Human Immunodeficiency Virus • Infectious Disease

Mass Balance and Absolute Oral Bioavailability of [14C]VH4524184 (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: ViiV Healthcare | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

First Time in Human Study of Long Acting VH4524184 Formulations (clinicaltrials.gov) - P1 | N=372 | Recruiting | Sponsor: ViiV Healthcare | N=268 ➔ 372

Enrollment change • Human Immunodeficiency Virus • Infectious Disease

223803: Mass Balance and Absolute Oral Bioavailability of [14C]VH4524184 (clinicaltrialsregister.eu) - P1 | N=9 | Recruiting | Sponsor: Viiv Healthcare UK Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Proof-of-Concept Phase 2a Trial of VH4524184 (VH-184), an Emerging Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile. (PubMed, Clin Infect Dis) - P2 | "VH-184 monotherapy demonstrated rapid and potent antiviral activity and a favorable safety and tolerability profile. The established exposure-response model and efficacy and safety results support further development of VH-184 as the core agent in complete ART regimens for HIV-1 (ClinicalTrials.gov, NCT06214052)."

Clinical • Journal • P2a data • Human Immunodeficiency Virus • Infectious Disease • CD4

Mass Balance and Absolute Oral Bioavailability of [14C]VH4524184 (clinicaltrials.gov) - P1 | N=9 | Not yet recruiting | Sponsor: ViiV Healthcare

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

223803: Mass Balance and Absolute Oral Bioavailability of [14C]VH4524184 (clinicaltrialsregister.eu) - P1 | N=9 | Not yet recruiting | Sponsor: Viiv Healthcare UK Limited

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

A Phase 2b Study Evaluating Oral VH4524184 Regimens in Treatment Naïve Persons With HIV-1 (INNOVATE Study) (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: ViiV Healthcare

Trial initiation date • Human Immunodeficiency Virus • Infectious Disease • CD4

A Phase 2b Study Evaluating Oral VH4524184 Regimens in Treatment Naïve Persons With HIV-1 (INNOVATE Study) (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: ViiV Healthcare | N=550 ➔ 150 | Trial primary completion date: May 2027 ➔ Sep 2027 | Not yet recruiting ➔ Recruiting

Enrollment change • Enrollment open • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

First Time in Human Study of Long Acting VH4524184 Formulations (clinicaltrials.gov) - P1 | N=268 | Recruiting | Sponsor: ViiV Healthcare | N=72 ➔ 268

Enrollment change • Human Immunodeficiency Virus • Infectious Disease

A Study to Evaluate VH4524184 Tablet Absorption, Effects of Food, and Interactions With Other Drugs in Healthy Adults (clinicaltrials.gov) - P1 | N=126 | Completed | Sponsor: ViiV Healthcare | Recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

A Study to Investigate Safety, Tolerability, and Pharmacokinetics (PK) of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity (clinicaltrials.gov) - P1 | N=84 | Completed | Sponsor: ViiV Healthcare | Recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

A Phase 2b Study Evaluating Oral VH4524184 Regimens in Treatment Naïve Persons With HIV-1 (INNOVATE Study) (clinicaltrials.gov) - P2 | N=550 | Not yet recruiting | Sponsor: ViiV Healthcare | Trial completion date: Mar 2029 ➔ Nov 2028

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

A Phase 2b Study Evaluating Oral VH4524184 Regimens in Treatment Naïve Persons With HIV-1 (INNOVATE Study) (clinicaltrials.gov) - P2 | N=550 | Not yet recruiting | Sponsor: ViiV Healthcare

New P2 trial • Human Immunodeficiency Virus • Infectious Disease

A Study to Evaluate VH4524184 Tablet Absorption, Effects of Food, and Interactions With Other Drugs in Healthy Adults (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: ViiV Healthcare | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

A Study to Evaluate VH4524184 Tablet Absorption, Effects of Food, and Interactions With Other Drugs in Healthy Adults (clinicaltrials.gov) - P1 | N=124 | Not yet recruiting | Sponsor: ViiV Healthcare

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

Phase 1 Evaluation of VH4524184, a Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile. (PubMed, Clin Infect Dis) - P1 | "These data support the safety and further development of VH-184 as a third-generation INSTI with long-acting potential for HIV-1 treatment (ClinicalTrials.gov, NCT05631704)."

Journal • P1 data • Human Immunodeficiency Virus • Infectious Disease

Proof-of-Concept Trial of VH4524184 (VH-184), a Third-Generation Integrase Strand Transfer Inhibitor (CROI 2025) - "An exposure-response relationship was established comparable to the maximum effect with other INSTIs. These results support further development of VH-184 as the core agent in a complete long-acting regimen for the treatment of HIV-1."

Human Immunodeficiency Virus • Infectious Disease

First Time in Human Study of Long Acting VH4524184 Formulations (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: ViiV Healthcare | Trial primary completion date: Mar 2027 ➔ Jan 2028

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

A Study to Investigate the Potential Drug-Drug Interaction Between VH4524184 and Oral Contraceptive (Loestrin) in Healthy Adult Female Participants (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: ViiV Healthcare | Recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

VH4524184 Proof-of-Concept in Treatment-Naïve Adults Living With HIV-1 (clinicaltrials.gov) - P2 | N=22 | Completed | Sponsor: ViiV Healthcare | Recruiting ➔ Completed | Trial completion date: Sep 2024 ➔ Jun 2024 | Trial primary completion date: Sep 2024 ➔ Jun 2024

Trial completion • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Phase 1 study of VH4524184 (VH-184), a new third-generation integrase strand transfer inhibitor (INSTI) with a unique resistance profile (AIDS 2024) - "We present the pharmacokinetics, safety, and in vitro resistance profile of VH-184. A double-blind, randomized, placebo-controlled, phase 1, first-time-in-human (FTIH) study evaluated oral VH-184 in healthy adults administered as single ascending doses (10-460 mg; part 1), multiple ascending doses (160-480 mg) for 14 days with concomitant midazolam (part 2), and as a single dose (100 mg) under fasted and fed conditions (part 3)...VH-184 demonstrated potent in vitro antiviral activity against dolutegravir-selected INSTI-resistant isolates (Figure). FTIH study results helped characterize VH-184 pharmacokinetics and indicate that VH-184 does not inhibit or induce CYP3A4 and has a moderate positive food effect. FTIH study results helped characterize VH-184 pharmacokinetics and indicate that VH-184 does not inhibit or induce CYP3A4 and has a moderate positive food effect. The in vitro resistance profile of VH-184 is distinct from prior INSTIs, retaining antiviral activity..."

P1 data • Human Immunodeficiency Virus • Infectious Disease • CYP3A4

In vitro characterization of VH4524184 (VH-184, S-365598), a new third-generation integrase strand transfer inhibitor (INSTI) with a unique resistance profile (AIDS 2024) - "The in vitro antiviral potency of VH-184 is comparable to DTG and CAB and its resistance profile is distinct from prior INSTIs. VH-184 is a third generation INSTI candidate with a superior resistance profile compared to DTG and CAB. These data support its further development for HIV-1 treatment."

Preclinical • Human Immunodeficiency Virus • Infectious Disease • CD4

First Time in Human Study of Long Acting VH4524184 Formulations (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: ViiV Healthcare | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2026 ➔ Jan 2028 | Trial primary completion date: Feb 2025 ➔ Mar 2027

Enrollment open • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease