Simplifed lenacapavir dosing: PK results in HIV negative study
3 August 2022. Related: Conference reports, Antiretrovirals, PK and drug interactions.
AIDS 2022 included a pharmacokinetic (PK) study of a simplified dosing strategy for the long-acting capsid inhibitor lenacapavir, currently being studied for both treatment and prevention. 
If confirmed, the new strategy could help adherence and reduce the number of clinic visits.
This phase 1 open-label study of HIV negative participants explored PK profiles from standard and simplified dosing strategies.
Group 1 (n=31) received the current three oral lead-in doses (600 mg on days 1 and 2, and 300 mg on day 8) before a sub-cutaneous (SC) injection (927 mg) on day 15.
Group 2 (n=14) used a simplified strategy with oral (600 mg) plus SC (927 mg) lenacapavir on day 1, followed by a second oral dose (600 mg) on day 2.
PK parameters were monitored from pre-dose to day 197. The target plasma concentration was 15.5 ng/mL, equivalent to 4x the protein adjusted IC90.
Mean plasma levels for group 1 were consistently above the target from 2 hours post-dose on day 2 until the final measurement on day 197. Tmax was reached 85 days post-SC injection.
Similar PK parameters were observed for the simplified regimen with concentrations consistently above the target from 2 hours post-dose on day 2 and an earlier Tmax at 70 days. However, the lower bound of the 95% CI dipped below the 4x pa IC90 threshold between days 168 and 182.
Participants were similar in each group, with median age about 32 years (range: 20 to 45) and median BMI was 26 kg/m2 (range: 22 to 30).
Adverse events were grade 1-2, mostly due to injection site reactions.
In HIV negative participants these PK profiles were comparable for simplified and standard dosing and remain above target levels for much of the study.
Median plasma concentrations remained above the 4x pa IC90 at all timepoints but results will need to be confirmed in people living with HIV as 90%CI dropped below this level with the simplified strategy. The lower levels between days 168 to 182 may be explained by the relatively low sample size (n=14) for group 2.
Lenacapavir has already been submitted to the EMA and US FDA for an indication in multidrug resistant HIV.
In July 2022, the EMA reported a positive recommendation for approval.
1. Jogiraju V et al. Pharmacokinetics of a simplified subcutaneous lenacapavir regimen versus phase 2/3 regimen. AIDS 2022 (Montreal). 29th July to 2nd August. Abstract PESUB22.
2. Lenacapavir gets positive opinion for approval in the EU to treat MDR HIV. HTB (July 2022)