Sunlenca (lenacapavir) / Gilead - LARVOL DELTA

Lenacapavir's success: Revitalizing antiviral drug discovery. (PubMed, Virulence) - No abstract available

Journal • Human Immunodeficiency Virus • Infectious Disease

Lenacapavir: a first-in-class capsid inhibitor for HIV treatment and prevention. (PubMed, Curr Opin Infect Dis) - "LEN is a novel agent that can be administered subcutaneously every 6 months. Approved for treatment-experienced adults with multidrug-resistant HIV, lenacapavir may have additional uses including for HIV prevention."

Journal • Human Immunodeficiency Virus • Infectious Disease

Cost-Effectiveness Analysis of Lenacapavir Compared to Cabotegravir and Generic Oral FTC/TDF for HIV Pre-Exposure Prophylaxis for Cis-Gender Women in the United States (ISPOR 2025) - "LEN is not cost-effective compared to generic FTC/TDF or CAB-LAI for HIV PrEP. However, LEN offers a viable alternative with reduced administration frequency for individuals at risk of acquiring HIV infection."

Clinical • Cost effectiveness • HEOR • Human Immunodeficiency Virus • Infectious Disease

Long-Acting Injectable Antiretroviral Therapy for Treatment of Human Immunodeficiency Virus: A Review. (PubMed, Curr HIV/AIDS Rep) - "Long-acting injectable (LAI) antiretroviral therapy (ART) for treatment of HIV-1 are approved both as a complete treatment regimen (cabotegravir/rilpivirine) and as an additional treatment option (lenacapavir) for those with multidrug resistant HIV-1. Here, we review the data supporting these approvals, pharmacokinetics, and additional patient populations that many benefit from LAI ART...LAI CAB/RPV is currently only approved in those with HIV-1 viral suppression, however recent data support the use of LAI ART in populations with adherence challenges. Furthermore, given high rates of NNRTI resistance globally, CAB/RPV is not recommended in low-and-middle income countries presently, although this recommendation is likely to change based on recently published data. More research is needed among groups that may benefit from long-acting treatments for HIV-1."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease

An HIV Vaccine in the Era of Twice-Yearly Lenacapavir for PrEP - Essential or Irrelevant? (PubMed, N Engl J Med) - No abstract available

Journal • Human Immunodeficiency Virus • Infectious Disease

Evaluation of Long-Acting Lenacapavir for the Treatment of HIV-1 in Treatment-experienced Adolescents and Children (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2026 ➔ Dec 2026 | Trial primary completion date: Mar 2026 ➔ Jun 2026

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

Impact of HIV-1 capsid polymorphisms on viral infectivity and susceptibility to lenacapavir. (PubMed, mBio) - "In this report, we investigated how HIV-1 sequence diversity within the LEN binding site may impact virus replication capacity and sensitivity to LEN. Our data demonstrate high capsid sequence conservation across a large and diverse collection of HIV-1 variants, with the majority of naturally occurring capsid polymorphisms having a detrimental effect on viral infectivity and minimal impact on susceptibility to LEN."

Journal • Human Immunodeficiency Virus • Infectious Disease

Structural and mechanistic bases for resistance of the M66I capsid variant to lenacapavir. (PubMed, mBio) - "The studies described here elucidate the underlying mechanism by which the M66I substitution confers a marked resistance to the inhibitor. Furthermore, our structural findings will aid future efforts to develop the next generation of capsid inhibitors with enhanced barriers to resistance."

Journal • Human Immunodeficiency Virus • Infectious Disease • CPSF6 • NUP153

Phenotypic Characterization of Replication-Impaired Lenacapavir-Resistant HIV Clinical Isolates. (PubMed, J Med Virol) - "All viruses with LEN RAMs remained sensitive to other HIV drug classes. Using a sensitive HIV-dependent reporter system enhanced our ability to assess the phenotypes of viruses with low RC, allowing for further investigation into LEN resistance and CA RAMs."

Journal • Human Immunodeficiency Virus • Infectious Disease

A new era in HIV treatment: Evaluating the benefits of lenacapavir. (PubMed, Int J STD AIDS) - No abstract available

Journal • Human Immunodeficiency Virus • Infectious Disease

The Need for Lenacapavir Compulsory Licences in Ending the HIV Epidemic. (PubMed, Clin Infect Dis) - "A coordinated response from governments, donors, civil society, and the private sector including Gilead is urgently required to ensure lenacapavir access is wide enough to eliminate HIV transmission worldwide. Unless crucial changes to the current license are made, compulsory licences may be required."

Journal • Human Immunodeficiency Virus • Infectious Disease

Lenacapavir for Human Immunodeficiency Virus (HIV) Prevention: A Commitment to Equitable Access and Partnership by Gilead Sciences. (PubMed, Clin Infect Dis) - "Gilead is committed to working with scientists, clinicians, communities, advocates, governments, and other stakeholders to achieve broad, sustainable global access to lenacapavir for HIV prevention, if approved. Lenacapavir holds potential for helping to end new HIV infections around the world, a potential that reflects the vision we have at Gilead: to end the HIV epidemic for everyone, everywhere."

Journal • Licensing / partnership • Human Immunodeficiency Virus • Infectious Disease

Quinazolinone-based Subchemotypes for Targeting HIV-1 Capsid Protein: Design and Synthesis. (PubMed, Med Chem Res) - "The recent FDA-approval of lenacapavir (LEN, GS-6207) and the subsequent discovery of GSK878 strongly validate HIV-1 capsid protein (CA) as a target for antiviral development...We have also worked out a modular synthesis of these novel subtypes. Although these new analogs only weakly inhibited HIV-1 and produced relatively small shifts in the thermal shift assay against pre-assembled CA hexamers, the design and synthesis reported herein inform future design and synthesis of structurally more elaborate analogs for improved potency."

Journal • Human Immunodeficiency Virus • Infectious Disease

Lenacapavir Plus Two Broadly Neutralizing Antibodies, Teropavimab and Zinlirvimab, for People With HIV-1 Highly Susceptible to Either Teropavimab or Zinlirvimab. (PubMed, J Infect Dis) - P1 | "More inclusive bNAb susceptibility criteria may be appropriate for future studies of this combination treatment."

Journal • Human Immunodeficiency Virus • Infectious Disease

Lenacapavir disrupts HIV-1 core integrity while stabilizing the capsid lattice. (PubMed, Proc Natl Acad Sci U S A) - "Our results suggest that LEN treatment does not prevent nuclear envelope docking but inhibits nuclear import of cores with or without loss of core integrity. In contrast, PF74 treatment blocks nuclear import by inhibiting the nuclear envelope docking of viral cores, highlighting their different mechanisms of nuclear import inhibition."

Journal • Human Immunodeficiency Virus • Infectious Disease

In men and gender-diverse persons, twice-yearly subcutaneous lenacapavir vs. daily oral F/TDF reduced HIV incidence. (PubMed, Ann Intern Med) - "GIM/FP/GP: [Formula: see text] Infectious Disease: [Formula: see text] Public Health: [Formula: see text]."

Journal • Human Immunodeficiency Virus • Infectious Disease

Successful treatment of MDR HIV infection with lenacapavir plus fostemsavir-based background regimen (ESCMID Global 2025) - No abstract available

Human Immunodeficiency Virus • Infectious Disease

Genetic diversity in the capsid protein-coding region of HIV-1 circulating in Angola: implications for primary resistance to the novel capsid inhibitor lenacapavir (ESCMID Global 2025) - No abstract available

Human Immunodeficiency Virus • Infectious Disease

Development of a Scalable Synthetic Route to (1R,5R)-2,2-Dimethoxybicyclo[3.1.0]hexan-3-one: An Important Intermediate in the Synthesis of Lenacapavir. (PubMed, Org Process Res Dev) - "This sequence affords (1R,5R)-2,2-dimethoxybicyclo[3.1.0]hexan-3-one in an overall 25% isolated yield as an enantiomerically pure compound. The entire process has been successfully demonstrated on a hundred-gram scale."

Journal

Susceptibility to Lenacapavir Among Newly Diagnosed HIV-Positive Patients Followed Up in Mozambique That Presented With Primary Antiretroviral Resistance to Other Classes. (PubMed, J Med Virol) - "Also, codon 66 was highly conserved. Our results support the potential effectiveness of lenacapavir as a PrEP regimen or rescue therapy for patients with at least one drug-resistance mutation."

Journal • Human Immunodeficiency Virus • Infectious Disease

First Clinical Data for Gilead’s Investigational Once-Yearly Lenacapavir for HIV Prevention Presented at CROI 2025 and Published in The Lancet (Businesswire) - P1 | N=40 | "Phase 1 Data Indicate Potential for Use of Once-Yearly Lenacapavir for HIV Prevention, with Plans to Launch a Phase 3 Trial in 2H 2025...The Phase 1 study evaluated the pharmacokinetics, safety and tolerability of two intramuscular single-dose 5000mg lenacapavir formulations....Lenacapavir plasma concentrations for participants remained above the 95% effective concentration for at least 56 weeks with both formulations. Furthermore, median trough concentrations of both formulations of once-yearly lenacapavir at Week 52 (57.0 ng/mL and 65.6 ng/mL) were higher than those observed with twice-yearly lenacapavir in the PURPOSE 1 and PURPOSE 2 trials at Week 26 (23.4 ng/mL). Data from the study confirmed that both once-yearly formulations of lenacapavir warrant further investigation....Medication-emergent adverse events were similar between the two cohorts and mostly mild to moderate in severity."

New P3 trial • P1 data • Human Immunodeficiency Virus

First Clinical Data for Gilead’s Investigational Once-Yearly Lenacapavir for HIV Prevention Presented at CROI 2025 and Published in The Lancet (Businesswire) - P3 | N=5,368 | PURPOSE-1 (NCT04994509) | Sponsor: Gilead Sciences | "New quantitative survey data and late-breaking qualitative survey data from the PURPOSE 1 trial...Additionally, at Week 52, most respondents (61%) reported they would feel more protected from HIV with twice-yearly PrEP injections compared with once-daily pills, and 61% of respondents also reported they would feel more confident about not missing a PrEP dose with twice-yearly injections compared with once-daily pills. Qualitative data among 108 participants also showed that respondents, particularly adolescents aged 16 and 17 years, noted that twice-yearly injections better suited their lifestyles compared with once-daily pills....The data showed that observed lenacapavir plasma concentrations were comparable between adolescent and adult trial groups, with participants in both groups experiencing the same most common adverse events. There were zero incident HIV infections across the adolescent and adult groups..."

Late-breaking abstract • P3 data • Human Immunodeficiency Virus

HIV PrEP Method Preferences Among Transgender and Gender-Diverse Adults in the United States (CROI 2025) - "Background The anticipated approval of lenacapavir for HIV pre-exposure prophylaxis (PrEP) may present an opportunity to better address inequitable PrEP implementation among priority populations in the United States (US)...Conclusions PrEP injection every two months was rarely selected as the most preferred method; and non-Latine Black and Latine individuals had higher odds of reporting that an injectable PrEP method administered every six months was their most preferred PrEP method. Future research should prioritize the development of implementation strategies that bolster comprehensive low-barrier PrEP services for non-Latine Black and Latine TGD adults, particularly TGD individuals for whom daily oral PrEP and injectable cabotegravir every two months are not desirable."

Clinical • Human Immunodeficiency Virus • Infectious Disease

Early PEPFAR Implementation of Cabotegravir-LA and Implications for Long-Acting HIV Prevention (CROI 2025) - "Background Despite the availability of oral HIV pre-exposure prophylaxis (PrEP), gaps remain in reaching the UNAIDS target of 21.2 million people on PrEP by the end of 2025 and reducing HIV incidence. Lessons learned from early CAB-LA introduction will inform continued scale-up of CAB-LA in additional PEPFAR-supported countries in 2025, with plans to reach 100,000 clients by the end of the year. This platform will also support future HIV prevention products including Lenacapavir."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

The HIV Epidemic Is Growing Faster in Countries Excluded From Gilead Voluntary Licenses (CROI 2025) - "Novel injectable pre-exposure prophylaxis (PrEP), lenacapavir (LEN), has superior efficacy to oral TDF/FTC. Rate of HIV acquisition has risen 55.3% in countries excluded since 2010, while falling 17% for included countries. If the imminent LEN VL includes all LMICs, this would cover 85% of the world's population, where 95% of new HIV acquisitions are diagnosed, facilitating affordable pricing of LEN as seen in LMICs included in the TAF VL."

Human Immunodeficiency Virus • Infectious Disease