Gilead Sciences announced positive topline results from the Phase 3 ARTISTRY-1 trial, demonstrating that its investigational single-tablet regimen combining bictegravir 75 mg and lenacapavir 50 mg (BIC/LEN) was statistically non-inferior to multi-tablet antiretroviral therapy regimens in virologically suppressed adults with HIV-1. The company plans to file Phase 3 data from the ARTISTRY trials with regulatory authorities and submit detailed findings for presentation at a future scientific congress.
Trial Design and Primary Results
ARTISTRY-1 (NCT05502341) is a multicenter Phase 2/3 open-label clinical trial that evaluated treatment responses in adults with HIV who switched from multi-tablet regimens to the investigational once-daily BIC/LEN combination. In the Phase 3 portion, participants were randomized 2:1 to receive the fixed-dose combination of bictegravir 75 mg/lenacapavir 50 mg or continue their stable baseline complex regimen.
The trial met its primary success criterion for non-inferiority to baseline multi-tablet antiretroviral therapy regimens. The primary efficacy endpoint was the percentage of participants with HIV-1 RNA levels ≤50 copies/mL at Week 48, as defined by the FDA snapshot algorithm. Key secondary endpoints at week 48 included the proportion of participants with virologic suppression (HIV viral load <50 copies/mL per US FDA Snapshot), change in baseline CD4 cell count, and the proportion of participants with treatment-emergent adverse events.
Addressing Unmet Medical Need
The trial addressed a significant unmet need for patients living with HIV-1 on complex regimens who cannot benefit from guideline-recommended single-tablet regimens due to pre-existing resistance, tolerability issues, and drug-drug interactions. These patients face challenges including high pill burden, complicated adherence, and reduced quality of life.
At baseline, participants enrolled in ARTISTRY-1 were taking between 2 and 11 pills per day for their HIV treatment, with approximately 40% taking their antiretrovirals more than once daily. This highlights the substantial pill burden that the investigational single-tablet regimen could potentially address.
"Developing new effective, convenient regimens for those left behind by advances in medical research is necessary to close the unmet HIV treatment gap," said Chloe Orkin, MBE, Clinical Professor of Infection and Inequities at Queen Mary University of London. "These ARTISTRY-1 trial results demonstrate that a combination regimen of bictegravir and lenacapavir maintains viral suppression in people living with HIV who would otherwise have to take a complex multi-tablet regimen. The findings are significant for those people, many of whom have lived with HIV for decades and who have medical comorbidities of aging and thus take many other medications as well."
Safety Profile
The BIC/LEN combination was generally well tolerated in the trial, with no significant or new safety concerns identified. This safety profile supports the potential for the combination to serve as a treatment option for patients requiring complex HIV regimens.
Drug Components and Mechanisms
Bictegravir is a global guideline-recommended integrase strand transfer inhibitor (INSTI) with a high barrier to resistance. INSTIs target the viral integrase and are used only in combination with other antiretroviral agents in HIV treatment.
Lenacapavir represents a first-in-class capsid inhibitor with a multi-stage mechanism of action that distinguishes it from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes. Lenacapavir is currently approved in multiple countries as pre-exposure prophylaxis (PrEP) and for treatment of multi-drug-resistant HIV in adults.
Ongoing Development Program
Further evaluation of this investigational combination includes the double-blind, Phase 3 ARTISTRY-2 (NCT06333808) trial, which is evaluating the safety and efficacy of switching from BIKTARVY (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets) to the fixed-dose combination of bictegravir 75 mg/lenacapavir 50 mg in virologically suppressed people with HIV-1. A topline data readout for the primary endpoint is anticipated before the end of the year.
"People living with HIV who are on complex antiretroviral treatment regimens may experience pill burden, adherence challenges and difficulties with the long-term management of HIV," said Jared Baeten, MD, PhD, Senior Vice President, Clinical Development, Virology Therapeutic Area Head, Gilead Sciences. "Gilead developed the first single-tablet complete regimen for the treatment of HIV in 2006. Today, innovative single-tablet regimens are still needed to help suit people's needs, modernizing treatment while helping to sustain viral suppression. By reducing the multi-tablet burden, we hope to improve health outcomes while expanding options."
Regulatory Status
Bictegravir and lenacapavir in combination are investigational and not approved anywhere globally. Their safety and efficacy have not been established in combination. The company plans to use Phase 3 results from both ARTISTRY-1 and ARTISTRY-2 trials to form the basis of regulatory submissions.
Lenacapavir has received significant recognition, being chosen as one of TIME's Best Inventions, recognized on Fortune's Change the World list, named the 2024 Breakthrough of the Year by the journal Science, and selected as the 2025 Prix Galien USA Award for Best Pharmaceutical Product.
