FDA Grants Priority Review for Bictegravir/Lenacapavir HIV Single-Tablet Regimen
FDA grants Priority Review for Gilead's bictegravir/lenacapavir single-tablet HIV regimen. The NDA is supported by ARTISTRY-1 and ARTISTRY-2 trials showing noninferiority. A PDUFA target date of August 27, 2026 has been set.
The US Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for bictegravir 75mg/lenacapavir 50mg (BIC/LEN), a once-daily, single-tablet regimen for the treatment of HIV-1 in adults who are virologically suppressed. A Prescription Drug User Fee Act target date of August 27, 2026 has been set for the application.
The combination therapy brings together bictegravir, an integrase strand transfer inhibitor (INSTI), and lenacapavir, a capsid inhibitor. The NDA is supported by data from the ARTISTRY-1 and ARTISTRY-2 trials.
ARTISTRY-1 included adults with HIV who were virologically suppressed (HIV-1 RNA <50 copies/mL) on complex regimens. Study participants (N=557) were randomly assigned 2:1 to switch to once-daily BIC/LEN (n=371) or continue on their stable baseline complex regimen (n=186). In the trial, 0.8% of patients treated with BIC/LEN had an HIV-1 RNA level of greater than or equal to 50 copies/mL compared with 1.1% of patients who continued on their baseline complex regimen, meeting the noninferiority margin. Additionally, treatment with BIC/LEN resulted in a 15mg/dL median reduction in total cholesterol vs a 2mg/dL median increase with the multi-tablet regimen.
ARTISTRY-2 included adults with HIV who were virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). Study participants (N=574) were randomly assigned 2:1 to switch to once-daily BIC/LEN (n=383) or continue B/F/TAF therapy (n=191). Treatment with BIC/LEN was noninferior to B/F/TAF, with 1.3% of patients treated with BIC/LEN presenting with an HIV-1 RNA level of 50 copies/mL or greater compared with 1.0% of those treated with B/F/TAF. CD4 cell count remained stable, and switching to BIC/LEN had no significant impact on body weight.
Findings from an ARTISTRY-2 resistance analysis (n=4; 2 patients from each treatment group) showed treatment-emergent resistance was not detected in 3 out of the 4 participants (1 BIC/LEN and 2 B/F/TAF participants) through week 48. One patient in the BIC/LEN group developed an isolated integrase substitution without phenotypic resistance. No capsid mutations were detected.
The primary endpoint for both trials was the proportion of patients with HIV-1 RNA greater than or equal to 50 copies/mL at week 48, as determined by the US FDA-defined snapshot algorithm (noninferiority margin: 4%).