lepetegravir (GS-1720)

Associated long-acting platforms

Oral solid form

Administration route

Oral

Therapeutic area(s)

Use case(s)

Use of drug

Dosage

Drug information

Delivery device(s)

Not provided

Scale-up prospects

Detailed manufacturing information is not currently available for this compound.

Tentative equipment list for manufacturing

Detailed manufacturing information is not currently available for this compound.

Manufacturing

Detailed manufacturing information is not currently available for this compound.

Specific analytical instrument required for characterization of formulation

Detailed manufacturing information is not currently available for this compound.

WONDERS2

Identifier

NCT06613685

Link

https://clinicaltrials.gov/study/NCT06613685

Phase

Phase II/III

Status

Terminated

Sponsor

Gilead Sciences

More details

The goal of this clinical study is to learn more about the experimental drugs GS-1720 (an oral, long-acting integrase strand transfer inhibitor (INSTI)) and GS-4182 (a prodrug of Lenacapavir (LEN)); to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy), to see if the combination of GS-1720 and GS-4182 is safe and if it works for treating human immunodeficiency virus type 1 (HIV-1) infection in treatment-naive people with HIV-1 (PWH). This study has two phases: Phase 2 and Phase 3. The primary objectives of this study are: Phase 2: To evaluate the efficacy of oral weekly GS-1720 coadministered with GS-4182 versus continuing Biktarvy (BVY) in treatment-naive PWH at Week 24. Phase

Purpose

Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2024-10-21

Anticipated Date of Last Follow-up
2026-03-26

Estimated Primary Completion Date
2029-01-01

Estimated Completion Date
2030-08-01

Actual Primary Completion Date
2026-03-16

Actual Completion Date
2026-03-16

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Key Inclusion Criteria: * HIV-1 RNA ≥ 500 copies/mL at screening. * Antiretroviral (ARV) treatment-naive, except the use of oral pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or F/TAF, up to 1 month prior to screening. Key Exclusion Criteria: * Prior use of any long acting parenteral antiretrovirals (ARVs) such as monoclonal antibodies, broadly neutralizing antibodies targeting HIV-1, LEN, injectable cabotegravir (including oral cabotegravir lead-in), and/or injectable rilpivirine. * Documented resistance to the integrase strand-transfer inhibitor class, specifically, resistance-associated mutations E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene. * Any of the follow

Health status

Study type

Interventional (clinical trial)

Enrollment

73

Allocation

Randomized

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

GS-US-544-5905

Identifier

NCT05585307

Link

https://clinicaltrials.gov/study/NCT05585307

Phase

Phase I

Status

Completed

Sponsor

Gilead Sciences

More details

Master protocol: The goal of this master clinical trial study is to learn how novel antiretrovirals (medicines that stop the virus from multiplying) affect the human immunodeficiency virus-1 (HIV-1) infection in people living with HIV (PWH). Substudy-01 (GS-US-544-5905-01) will evaluate bavtavirine in PWH. Substudy-02 (GS-US-544-5905-02) will evaluate GS-1720 in PWH. Substudy-03 (GS-US-544-5905-03) will evaluate GS-6212 in PWH.

Purpose

Study of Novel Antiretrovirals in Participants With HIV-1

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2022-10-26

Anticipated Date of Last Follow-up
2024-07-30

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2024-02-17

Actual Completion Date
2024-03-08

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Key Inclusion Criteria: All Substudies: * Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 5000 copies/mL but ≤ 400,000 copies/mL at screening. * Cluster of differentiation 4 (CD4) cell count \> 200 cells/mm\^3 at screening. * Antiretroviral (ARV) treatment-naive or treatment-experienced but naive to the investigational ARV drug class being investigated in the given substudy and have not received any ARV within 12 weeks of screening, including medications received for pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) (note that current or prior receipt of long acting (LA) parenteral ARVs such as monoclonal antibodies (mAbs) targeting HIV-1, injectable cabotegravir (CAB), or injectable rilpivirine (RPV) is exclusionary). * Have adequate renal function

Health status

Study type

Interventional (clinical trial)

Enrollment

49

Allocation

Non-randomized

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

WONDERS1

Identifier

NCT06544733

Link

https://clinicaltrials.gov/study/NCT06544733

Phase

Phase II/III

Status

Suspended

Sponsor

Gilead Sciences

More details

The goal of this clinical study is to learn more about the experimental drugs GS-1720 and GS-4182; to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY), to see if the combination of GS-1720 and GS-4182 is safe and if it works for treating human immunodeficiency virus type 1 (HIV-1) infection. This study has two phases: Phase 2 and Phase 3. The primary objectives of this study are: Phase 2: To evaluate the efficacy of switching to oral weekly GS-1720 in combination with GS-4182 versus continuing BVY in virologically suppressed people with HIV-1 (PWH) at Week 24. Phase 3: To evaluate the efficacy of switching to oral weekly GS-1720/GS-4182 Fixed-dose combination (FDC) tablet regimen ve

Purpose

Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2024-08-20

Anticipated Date of Last Follow-up
2025-09-22

Estimated Primary Completion Date
2028-01-01

Estimated Completion Date
2029-06-01

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Key Inclusion Criteria: * Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 24 weeks before and at screening. * Receiving BVY for ≥ 24 weeks prior to screening. Key Exclusion Criteria: * Prior use of, or exposure to LEN, GS-1720, or GS-4182. * History of virologic failure while on an integrase strand-transfer inhibitor (INSTI)-based regimen. * Documented integrase strand-transfer inhibitor (INSTI) resistance, specifically, resistance-associated mutations (RAMs) E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene. * Prior use of any long-acting (LA) parenteral antiretrovirals (ARV) such as monoclonal antibodies (mAbs) or broadly neutralizing antibodies (bNAbs) targeting HIV-1, injectable cabotegravir (including oral cabotegravir lead-in), or injecta

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

675

Allocation

Randomized

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

Proprietary excipients used

Not provided

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

Not provided

Residual solvents used

Not provided

Compound patent families

Publications

P035 Pharmacokinetic/pharmacodynamic and resistance analyses of GS-1720, a once-weekly oral integrase strand transfer inhibitor, Brie Falkard et al. HIV Glasgow, 10-13 Nov. 2024

Background: Long-acting oral antiretrovirals remain an unmet medical need. GS-1720 is an oral integrase strand transfer inhibitor (INSTI) with potent anti-HIV-1 activity. In a phase Ib study in people with HIV-1, GS-1720 was well tolerated and demonstrated antiviral activity (mean reduction in HIV-1 RNA across four dosing cohorts [30, 150, 450 and 900 mg] of 1.74−2.44 log10 copies/ml from baseline to day [D] 11) [1], comparable with approved once-daily INSTIs. We report GS-1720 pharmacokinetics/pharmacodynamics and resistance data from this phase Ib study.

Methods: In this open-label multicohort study, participants, who were treatment-naïve or treatment-experienced but naïve to INSTIs and off antiretroviral therapy for ≥12 weeks, were administered oral GS-1720 on D1 and D2 and followed for 10 days. Participants were tested for genotypic and phenotypic integrase (IN) resistance at baseline and D11. Endpoints included: change in HIV-1 RNA (log10 copies/ml) from baseline to D11 [1], GS-1720 concentrations on D11, correlation between concentrations at D11 versus reduction of plasma HIV-1 RNA, emergence of IN resistance mutations at D11.

Results: Participants were enrolled into 30, 150, 450 and 900 mg cohorts (n = 28; 7/cohort). Median (range) age was 33 (18–62) years; 89.3% were male. Mean GS-1720 concentrations on D11 were 1.64, 5.87, 8.78 and 18.4 µg/ml in 30, 150, 450 and 900 mg cohorts, respectively; mean HIV-1 RNA reductions on D11 were 1.74, 2.18, 2.44 and 2.37 log10 copies/ml, respectively. In participants with GS-1720 concentrations at D11 above two-fold the inhibitory quotient (IQ2; 3.876 µg/ml), robust antiviral activity (≥1.5 log10 copies/ml reduction in HIV-1 RNA from baseline to D11) was observed. No participant had primary resistance-associated mutations (RAMs) in IN at screening. No resistance to the INSTI-class was detected at D11. One individual (lowest dose [30 mg] cohort) had increasing HIV-1 RNA after D7 of the monotherapy period. However, resistance testing showed no INSTI RAMs at D11.

Conclusions: 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.

Reference

1. Fichtenbaum CJ, Berhe M, Bordon J, Lalezari JP, Oguchi G, Sinclair G, et al. Antiviral activity, safety, and pharmacokinetics of GS-1720, a novel weekly oral INSTI [CROI Abstract 116]. Top Antivir Med. 2024;32(1):19.

Additional documents

No documents were uploaded

Useful links

• Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated (WONDERS2) - Gilead's clinical trials website

• Gilead Provides Update on Clinical Studies Evaluating GS-1720 and/or GS-4182 for the Treatment of HIV-1 Infection - on hold

	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 Not provided
	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 Not provided
	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 Not provided

GS-1720 is on the priority list of MPP since March 2025, as a candidate for which voluntary licensing and technology transfer through MPP would lead to expanded access, significant health benefits, and substantial public health impact compared to available standards of care (https://medicinespatentpool.org/progress-achievements/prioritisation#pills-hiv)