Investigational Bictegravir–Lenacapavir Single-Tablet Regimen Noninferior to Standard Therapy in Phase 3 ARTISTRY-2 Trial

Gilead Sciences announced positive topline results from the Phase 3 ARTISTRY-2 trial evaluating an investigational once-daily, single-tablet regimen combining bictegravir and lenacapavir for the treatment of adults with HIV who are virologically suppressed. The regimen met the primary endpoint for noninferiority compared with a standard-of-care bictegravir-based regimen containing emtricitabine and tenofovir alafenamide, according to a December 15, 2025, press release.¹

ARTISTRY-2 was a multicenter, double-blind, randomized Phase 3 study (NCT06333808) in which adults with HIV who were virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide were randomized 2:1 either to switch to bictegravir 75 mg/lenacapavir 50 mg or to continue their existing regimen. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48, assessed using the US Food and Drug Administration (FDA) snapshot algorithm.¹

At Week 48, the investigational bictegravir/lenacapavir regimen met the predefined criterion for noninferiority. The combination was generally well tolerated, and no significant or new safety concerns were identified during the trial, according to Gilead.¹

Key secondary endpoints at Week 48 included the proportion of participants with virologic suppression (HIV-1 RNA <50 copies/mL per the FDA snapshot algorithm), change from baseline in CD4 cell count, and the proportion of participants experiencing treatment-emergent adverse events.¹

“The findings from ARTISTRY-2 provide evidence that the investigational combination of bictegravir—a standard-of-care integrase strand transfer inhibitor—and lenacapavir—a novel capsid inhibitor—has a comparable efficacy profile to a global guideline-recommended treatment regimen, demonstrating potential to expand current HIV treatment options,” Eric Meissner, MD, PhD, associate professor and director of HIV and Hepatitis Patient Care and Research at the Medical University of South Carolina, stated in the press release.¹

The investigational regimen combines bictegravir, an integrase strand transfer inhibitor with a high barrier to resistance, and lenacapavir, a first-in-class capsid inhibitor with no overlapping resistance to other existing antiretroviral drug classes. A fixed-dose, single-tablet regimen of these agents could offer an additional option for maintaining virologic suppression in adults with HIV, according to the company.¹

“These data support the potential of BIC/LEN as a meaningful additional treatment option for adults with HIV who are virologically suppressed,” Jared Baeten, MD, PhD, senior vice president of clinical development and virology therapeutic area head at Gilead Sciences, said in the press release. “We look forward to sharing the full Phase 3 data from the ARTISTRY-1 and ARTISTRY-2 trials next year and submitting these data for regulatory approval.”¹

The ARTISTRY-2 results will be combined with findings from the Phase 3 ARTISTRY-1 trial (NCT05502341) to support planned regulatory submissions. Topline results from ARTISTRY-1, announced in November 2025, showed that the investigational bictegravir/lenacapavir regimen was well tolerated and statistically noninferior to multi-tablet antiretroviral regimens.²

Bictegravir and lenacapavir in combination remain investigational and are not approved anywhere globally. The safety and efficacy of this combination have not been established by the US FDA.¹

References:

1. Gilead’s investigational single-tablet regimen of bictegravir and lenacapavir for HIV treatment meets primary endpoint in phase 3 ARTISTRY-2 trial. Gilead. News release. December 15, 2025. Accessed December 16, 2025. https://investors.gilead.com/news/news-details/2025/Gileads-Investigational-Single-Tablet-Regimen-of-Bictegravir-and-Lenacapavir-for-HIV-Treatment-Meets-Primary-Endpoint-in-Phase-3-ARTISTRY-2-Trial/default.aspx
2. Gilead’s investigational single-tablet regimen of bictegravir and lenacapavir for HIV-1 treatment meets primary endpoint in phase 3 ARTISTRY-1 trial. Gilead. News release. November 13, 2025. Accessed December 16, 2025. https://www.gilead.com/news/news-details/2025/gileads-investigational-single-tablet-regimen-of-bictegravir-and-lenacapavir-for-hiv-1-treatment-meets-primary-endpoint-in-phase-3-artistry-1-trial