PII-056 - LENACAPAVIR PHARMACOKINETICS AND DDI POTENTIAL WITH CO-ADMINISTERED ANTIRETROVIRALS IN PEOPLE WITH HIV.

V. Jogiraju¹, M. Shelton², P. Dheri², J. Ling², H. Wang², H. Dvory-Sobol², M. Rhee², R. Palaparthy¹, R. Singh¹; ¹Gilead Sciences, Foster City, CA, USA, ²Bioscience Communications, Foster City, CA, USA.

Background: Lenacapavir (LEN), a potent, first-in-class, HIV-1 capsid inhibitor, is in development for the treatment and prevention of HIV-1. In ongoing Phase 2/3 studies (CAPELLA and CALIBRATE), LEN in combination with other antiretrovirals led to high rates of virologic suppression and was well tolerated. Our objective was to characterize the pharmacokinetics (PK) of LEN in CAPELLA and CALIBRATE.

Methods: In both clinical studies (n=175), people with HIV-1 (PWH) received oral LEN loading (600 mg on Days 1 and 2; 300 mg on Day 8) followed by 927 mg subcutaneous (SC) injection on Day 15 in an every 6 month regimen (Q6M). In CAPELLA, LEN was administered with an optimized background regimen. In CALIBRATE, LEN was used with emtricitabine/tenofovir alafenamide (F/TAF) for 28 weeks, then switched to TAF or bictegravir (BIC). LEN PK was evaluated for 1 year in both studies. Noncompartmental analysis was conducted for PK of TAF, tenofovir (TAF metabolite) and BIC to assess drug-interactions with LEN.

Results: In both studies, mean LEN concentration and the lower bound 90% confidence interval (CI) reached the efficacy target (inhibitory quotient of 4 [IQ4] = 15.5 ng/mL) by Day 2 and sustained above IQ4 through 6 months and 1 year. Accumulation of ~1.2-fold was observed at the end of 1 year (steady state). TAF (P-gp substrate) exposures were 24-32% higher in the presence of LEN (weak P-gp inhibitor). There were no clinically relevant changes in plasma exposures of BIC.

Conclusion: In PWH, targeted exposures (ie, lower bound 90% CI of the mean Ctrough ≥IQ4) were achieved rapidly after dosing initiation and were maintained through the end of the dosing interval at 6 months and 1 year. LEN exhibited minimal accumulation over the dosing period of 1 year. No clinically relevant drug interactions were noted with TAF or BIC.