Drug name
Last update: Apr 2026Lenacapavir pacfosacil (GS-4182)
Developer(s)
Drug information
Not provided
GS-4182
investigational
Small molecule
Prodrug of lenacapavir (capsid inhibitor)
GS-4182 is an investigational lenacapavir prodrug with improved bioavailability and potential for oral weekly administration. The chemical structure of GS-4182 is not yet available in the public domain. GS-4182 is studied in combination with GS-1720, a new oral INSTI. Phase II/III WONDERS trials are currently underway using the GS-4182+GS-1720 combination. If successful, a weekly oral HIV treatment could provide a valuable alternative for PLHIV.
GS-4182 is currently in clinical development and not yet approved in any jurisdiction.
GS-4182 is currently in clinical development and not yet approved in any jurisdiction.
Therapeutic area(s)
- HIV
- Treatment
Administration route
Oral
Associated long-acting platforms
Oral solid form
Use of drug
- Self-administered
- Other/Variable/Unknown : once a week oral dosing with GS-1720 is the investigated schedule
- Weekly
In June 2025, FDA has paused the clinical trials of GS-4182 and GS-1720 combination due to decrease in CD4 T-cell count and absolute lymphocyte count.
Dosage
300mg is the investigated dose
600mg is the investigated loading dose (2 tablets)
In the phase 2/3 study (NCT06613685), participants will receive a 1-day loading dose of GS-1720 (1300 mg) and GS-4182 (600 mg) on Day 1.Thereafter, participants will take weekly doses of single agent GS-1720 (650 mg) and GS-4182 (300 mg) co-administered for at least 48 weeks.
Not provided
Not provided
Associated technologies
Not provided
Comment & Information
Developer(s)
Gilead Sciences, Inc.
Gilead Sciences, founded in 1987 by Dr. Michael Riordan, began with a focus on oligonucleotide-based therapies. It evolved into a leader in antiviral research, developing breakthrough treatments for HIV, hepatitis B and C, and COVID-19. Headquartered in Foster City, California, Gilead also invests in oncology, inflammation, and cell therapy.
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
GS-4182 (lenacapavir pacfosacil) and GS-1720 (lepetegravir) combination and tablet formulation
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.
WO2026020086
Combination, formulation
Gilead
Not provided
July 18, 2045
Not yet in national phase
Lenacapavir pacfosacil tablet formulation
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.
WO2026006521
Formulation
Gilead
Not provided
June 26, 2045
Not yet in national phase
Lenacapavir pacfosacil preparation process (Formula I)
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).
WO2024249672
Process
Gilead
Not provided
May 30, 2044
Pending: AU, BR, CA, CN, EP, IN, JP, KR, US
Polymorphs of lenacapavir pacfosacil (Compound 1)
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
WO2024249573
Polymorphs
Gilead
Not provided
May 30, 2044
Pending: AU, BR, CA, CN, EP, IN, JP, KR, US
Lenacapavir pacfosacil compound and analogues
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.
WO2023102239
Compound
Gilead
Not provided
December 2, 2042
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.
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Useful links
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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
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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