GS-1720 / Gilead - LARVOL DELTA

FDA slaps clinical hold on multiple Gilead HIV combo therapy trials, shares fall (FierceBiotech) - "Gilead has been hit with a clinical hold from the FDA for five tests of its experimental HIV combination treatment amid safety concerns...the California Big Pharma said trials of GS-1720, an investigational integrase strand transfer inhibitor, and/or GS-4182, an investigational capsid inhibitor, had been put on a full FDA hold. The drugs had been in two phase 2/3 tests known as WONDERS-1 and WONDERS-2, as well as three earlier phase 1 studies...The hold comes after “the identification of a safety signal of decreases in CD4+T-cell (CD4) and absolute lymphocyte counts in a subset of participants receiving the combination of GS-1720 and GS-4182,” Gilead said in its statement."

FDA event • Trial suspension • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated (clinicaltrials.gov) - P2/3 | N=675 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

In Vitro Resistance Profile for GS-1720, a Potent Once-Weekly Oral InSTI in Clinical Development (CROI 2025) - "Results GS-1720 retained potent antiviral activity, defined as an EC50 fold-change (FC) 300, 140 and 119 days in culture, respectively...In a fixed-dose viral breakthrough assay, clinically relevant concentrations of GS-1720 or BIC prevented viral breakthrough while EVG and raltegravir, when tested at their equivalent clinical trough plasma concentrations, showed breakthrough with resistance in 45% and 18% of PBMC cultures (n=44-48/condition), respectively. Conclusions GS-1720 exhibits an in vitro resistance profile comparable to the best-in-class INSTI bictegravir, including high barrier to resistance and minimal cross-resistance within the INSTI class. These observations support the ongoing clinical development of GS-1720 as a novel once-weekly oral INSTI."

Preclinical • Human Immunodeficiency Virus • Infectious Disease

(H-01) HIV Resistance to bNAbs, Cabotegravir, GS 1720, and Other Agents (CROI 2025) - No abstract available

Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed (clinicaltrials.gov) - P2/3 | N=675 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Pharmacokinetic/pharmacodynamic and resistance analyses of GS‐1720, a once‐weekly oral integrase strand transfer inhibitor (HIV-Glasgow 2024) - "GS-1720 showed robust antiviral activity with D11 concentrations above IQ2. There were no observed cases of treatment-emergent IN resistance, including participants with low GS-1720 concentrations. The robust pharmacokinetics/pharmacodynamics data and lack of resistance support further clinical development and dose selection for GS-1720."

PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated (clinicaltrials.gov) - P2/3 | N=675 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Pharmacokinetics and Safety of GS-1720 Following Multiple Ascending Doses in a Phase 1a Study in People Without HIV-1 (IDWeek 2024) - No abstract available

Clinical • P1 data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated (clinicaltrials.gov) - P2/3 | N=675 | Not yet recruiting | Sponsor: Gilead Sciences

Combination therapy • New P2/3 trial • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed (clinicaltrials.gov) - P2/3 | N=675 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed (clinicaltrials.gov) - P2/3 | N=675 | Not yet recruiting | Sponsor: Gilead Sciences

Combination therapy • New P2/3 trial • Human Immunodeficiency Virus • Infectious Disease

Nonclinical pharmacology profile of GS-1720, a novel highly potent once-weekly oral HIV-1 integrase strand transfer inhibitor in clinical development (AIDS 2024) - "When tested against a panel of INSTI-resistant HIV-1 mutants, the EC50 fold-change range relative to wild-type virus for GS-1720, bictegravir, and elvitegravir was 0.9 to 8.5, 0.6 to 4.0, and 5.1 to >86, respectively...GS-1720 demonstrated no antiviral antagonism when combined with other antiretrovirals, including lenacapavir, and showed no activity against HBV, HCV, HSV-2 or SARS-CoV-2 and low cytotoxicity in all tested human cell types. GS-1720 is a novel oral INSTI with significantly improved antiviral potency compared to bictegravir and a similar nonclinical virology, pharmacology and safety profile. Overall, these data support the ongoing clinical development of GS-1720 as a component of a novel once-weekly oral regimen for HIV-1 treatment."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4

Phase 1a safety and pharmacokinetics of single ascending doses of oral GS-1720 in people without HIV-1 (AIDS 2024) - "GS-1720 was well tolerated across the doses tested and exhibited a nonlinear PK with a half-life supportive of once-weekly oral dosing. The emerging safety and PK data from this study were used to inform dose selection for Phase 1b and Phase 2 studies."

Clinical • P1 data • PK/PD data • Fatigue • Human Immunodeficiency Virus • Infectious Disease

Study of Novel Antiretrovirals in Participants With HIV-1 (clinicaltrials.gov) - P1 | N=49 | Completed | Sponsor: Gilead Sciences | Active, not recruiting ➔ Completed | Trial completion date: Mar 2027 ➔ Mar 2024 | Trial primary completion date: Mar 2027 ➔ Mar 2024

Trial completion • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Study of Novel Antiretrovirals in Participants With HIV-1 (clinicaltrials.gov) - P1 | N=49 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting | N=110 ➔ 49 | Trial completion date: Dec 2024 ➔ Mar 2027 | Trial primary completion date: Dec 2024 ➔ Mar 2027

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

Study of Novel Antiretrovirals in Participants With HIV-1 (clinicaltrials.gov) - P1 | N=110 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: May 2024 ➔ Dec 2024 | Trial primary completion date: May 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Antiviral Activity, Safety, and Pharmacokinetics of GS-1720: A Novel Weekly Oral InSTI (CROI 2024) - "GS-1720 demonstrated potent antiviral activity and PK supportive of once weekly oral dosing while being well-tolerated. The observed >2 log…10 copies/mL decline in HIV-1 RNA and half-life >1 week in this cohort demonstrates the potential of GS-1720 as part of an oral weekly INSTI-based regimen."

Clinical • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Study of Novel Antiretrovirals in Participants With HIV-1 (clinicaltrials.gov) - P1 | N=110 | Recruiting | Sponsor: Gilead Sciences | Phase classification: P1b ➔ P1

Phase classification • Human Immunodeficiency Virus • Infectious Disease • CD4