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Gilead's ARTISTRY-1 Phase III Trial Unveils Promising Data for HIV-1 Treatment

On November 13, Gilead Sciences announced positive topline results from the Phase III ARTISTRY-1 trial for its investigational single-tablet regimen combining Bictegravir (BIC) and Lenacapavir (LEN) for the treatment of HIV-1. This open-label trial evaluated the efficacy of transitioning from multi-tablet regimens to the BIC/LEN regimen for adults who had achieved virological suppression.

The results demonstrate that the BIC/LEN regimen exhibited statistical non-inferiority compared to existing multi-tablet regimens, offering a new therapeutic option that may ease the burden of treatment for adults living with HIV-1. The ARTISTRY trial results are expected to support regulatory submissions, with detailed findings to be presented at upcoming conferences.

Key Efficacy Metrics and Tolerability

In the ARTISTRY-1 trial, participants on the once-daily BIC/LEN were assessed against a baseline of multi-tablet antiretroviral therapy. The primary efficacy endpoint measured the proportion of participants who remained virologically suppressed (with an HIV viral load of over 50 copies/mL) at 48 weeks, utilizing the FDA's Snapshot Algorithm. The tolerability of BIC/LEN was generally good, with no significant safety concerns emerging during the trial.

Patients previously on complex regimens often face challenges due to existing drug resistance, tolerability issues, and the burden of taking multiple pills, which can lead to adherence difficulties and reduced quality of life. The new BIC and LEN single-tablet regimen provides a potential solution by simplifying treatment for those navigating the complexities of HIV medication.

ARTISTRY-1 participants were taking between two to eleven pills daily prior to switching to BIC/LEN, with around 40% needing multiple doses of their antiretroviral therapy. Chloe Orkin, MBE, a Clinical Professor of Infectious Diseases at Queen Mary University of London, emphasized the necessity of effective, user-friendly regimens to address unmet needs in HIV treatment. She highlighted that the results indicate that the combination of BIC and LEN can maintain viral suppression in HIV-positive individuals who struggle with complex multi-tablet regimens, many of whom have been living with HIV for decades and often require several concurrent medications due to comorbid conditions as they age.

Trial Design and Methodology

The ARTISTRY-1 trial (NCT05502341) was an international study comparing the BIC/LEN regimen to existing complex multi-tablet regimens among HIV-positive individuals who had previously maintained virological suppression. In this clinical trial, subjects were randomized in a 2:1 ratio to receive either the fixed-dose combination of Bictegravir 75 mg and Lenacapavir 50 mg or to stay on their stable multi-tablet regimen. The main assessment was the proportion of participants who failed to maintain virological suppression at 48 weeks. Secondary endpoints included the percentage of participants achieving virological suppression, changes in CD4 cell counts, and the incidence of treatment-emergent adverse events (TEAEs).

Jared Baeten, MD, PhD, Gilead's Senior Vice President of Clinical Development for Infectious Diseases, stated that people with complex antiretroviral regimens often grapple with adherence issues, medication burden, and challenges related to long-term management of HIV. He added that Gilead pioneered the development of the first single-tablet regimen for HIV treatment in 2006 but acknowledged the ongoing need for innovative single-tablet regimens that can effectively meet patients' needs while achieving sustained viral suppression.

Future Prospects: ARTISTRY-2 Trial

To further evaluate the fixed-dose combination, Gilead is conducting a double-blind Phase III trial, ARTISTRY-2 (NCT06333808), assessing the safety and efficacy of transitioning from Biktarvy (Bictegravir 50 mg/Emtricitabine 200 mg/Tenofovir Alafenamide 25 mg) to the BIC/LEN regimen among virally suppressed HIV-1 positive participants. Topline data for the primary endpoint is expected to be announced by the end of the year.

Currently, the combination of Bictegravir and Lenacapavir is under investigation and has not yet received worldwide regulatory approval. Their safety and efficacy remain to be fully established.

Current Landscape for HIV Treatment

At present, there is still no cure for HIV or AIDS. Bictegravir is an integrase inhibitor recommended for use in combination with other antiretrovirals, while Lenacapavir is approved in several countries as a pre-exposure prophylaxis (PrEP) to reduce the risk of sexually transmitted HIV for at-risk adults and adolescents. Lenacapavir also shows promise as a treatment option for multidrug-resistant HIV-positive individuals when used with other HIV medications, with a mechanism that disrupts multiple stages of the HIV life cycle.

Gilead has been a leader in HIV treatment for over 35 years, having developed 13 different therapies that have significantly improved health outcomes for people living with HIV. Their commitment to scientific innovation aims to meet the evolving needs of HIV positive individuals worldwide, contributing to the global effort to end the HIV epidemic. Gilead is also recognized as a major philanthropic contributor to HIV-related initiatives, reinforcing their mission to enhance access to care and reduce barriers to treatment for HIV patients everywhere.

As the ongoing ARTISTRY trials progress, the healthcare community remains hopeful for breakthroughs that can further simplify and enhance HIV treatment regimens, ultimately improving the quality of life for those affected by this virus.