Lenacapavir pacfosacil (GS-4182)

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

Not provided

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

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
2024-12-26

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

Description

GS-4182 (lenacapavir pacfosacil) and GS-1720 (lepetegravir) combination and tablet formulation

Brief description

The disclosure provides methods of treating and/or preventing HIV infections using a Compound 1, or a pharmaceutically acceptable salt thereof, and a Compound 2, or a pharmaceutically acceptable salt thereof. The disclosure further provides pharmaceutical formulations, particularly solid oral dosage forms comprising a Compound 1, or a pharmaceutically acceptable salt thereof, and a Compound 2, or a pharmaceutically acceptable salt thereof.

Representative patent

WO2026020086

Category

Combination, formulation

Patent holder

Gilead

Exclusivity

Not provided

Expiration date

July 18, 2045

Status

Not yet in national phase

Description

Lenacapavir pacfosacil tablet formulation

Brief description

The present disclosure relates to pharmaceutical formulations comprising a HIV capsid inhibitor and methods for the treatment or prevention of a human immunodeficiency virus (HIV) infection in a patient.

Representative patent

WO2026006521

Category

Formulation

Patent holder

Gilead

Exclusivity

Not provided

Expiration date

June 26, 2045

Status

Not yet in national phase

Description

Lenacapavir pacfosacil preparation process (Formula I)

Brief description

The present disclosure relates generally to processes for preparing a compound useful in the prevention or treatment of a Retroviridae viral infection, including an infection caused by the human immunodeficiency virus (HIV).

Representative patent

WO2024249672

Category

Process

Patent holder

Gilead

Exclusivity

Not provided

Expiration date

May 30, 2044

Status

Pending: AU, BR, CA, CN, EP, IN, JP, KR, US

Description

Polymorphs of lenacapavir pacfosacil (Compound 1)

Brief description

The present disclosure relates to solid forms of compounds and pharmaceutical compositions thereof, which are useful in the treatment and prevention of a Retroviridae viral infection including an infection caused by the HIV virus

Representative patent

WO2024249573

Category

Polymorphs

Patent holder

Gilead

Exclusivity

Not provided

Expiration date

May 30, 2044

Status

Pending: AU, BR, CA, CN, EP, IN, JP, KR, US

Description

Lenacapavir pacfosacil compound and analogues

Brief description

The present disclosure relates generally to certain compounds, pharmaceutical compositions comprising said compounds, and methods of making and using said compounds and pharmaceutical compositions. The compounds and compositions provided herein may be used for the treatment or prevention of a Retroviridae infection, including an HIV infection.

Representative patent

WO2023102239

Category

Compound

Patent holder

Gilead

Exclusivity

Not provided

Expiration date

December 2, 2042

Status

Granted: US Pending: AE, AP, AR, AU, BH, BR, CA, CO, CL, CN, CR, DO, EA, EG, EP, GT, HK, ID, IN, IL, JP, KR, KW, MX, MY, NG, NZ, OM, PA, PE, PH, QA, TH, TW, UA, VN, ZA

Publications

Hoffmann C, Rockstroh JK. Standardisation of monitoring routines for new long-acting antiretrovirals in development. Lancet HIV. 2026;13(4):e282-e286. doi:10.1016/S2352-3018(25)00329-7

The US Food and Drug Administration's clinical hold on Gilead Sciences' once-weekly combination of GS-1720 and GS-4182 due to unexpected CD4 T-cell and lymphocyte count declines represents a key safety signal in long-acting HIV therapy development. This event parallels the earlier islatravir trials, in which similar immunological effects led to a downsized development programme with lower doses of the drug. The current safety signal must involve different mechanisms, as the combination contains an integrase inhibitor and a capsid inhibitor rather than a nucleoside reverse transcriptase translocation inhibitor. Although GS-1720 appears well tolerated in early studies, the high doses used might have contributed to toxicity. As GS-4182 is a prodrug that converts to lenacapavir, the parent compound warrants careful evaluation, particularly given lenacapavir's anticipated widespread use for HIV prevention. Existing lenacapavir data show favourable safety profiles. However, CD4 T-cell reporting has been inconsistent across trials, and different study populations and dosing regimens might not fully capture all potential immunological effects. CD4 T-cell declines represent a key concern for people with HIV. Future trials should implement standardised monitoring protocols with individual participant trajectories, predefined decline thresholds, and clear discontinuation criteria. As long-acting antiretroviral therapy advances, maintaining rigorous immunological surveillance becomes essential to balance dosing convenience against potential immunological risks.

Additional documents

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Useful links

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	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

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