Pharmacological outlook of Lenacapavir: a novel first-in-class Long-Acting HIV-1 Capsid Inhibitor
Giovanni Di Perri
Abstract
studies and the 10-day monotherapy clinical study with single injections. The antiretroviral activity of Lenacapavir is unaffected by any mutation conferring resistance to older antiretrovirals. Lenacapavir is slowly released from the site of injection and this requires an initial coverage by its oral formulation (half-life: 10-12 days) in order to provide adequate pharmacokinetic exposure in the first days of treatment. The subcutaneous administration of Lenacapavir (half-life: 8-12 weeks) is then scheduled every 6 months. Lenacapavir is metabolized by CYP3A and UGT1A1, it is a substrate of Pgp and a moderate inhibitor of CYP3A. While co-administration with strong inducers of these enzymatic entities is contraindicated or it is not recommended in case of weaker inducers, few are the potential interactions of Lenacapavir as perpetrator (by its moderate inhibitory effect on CYP and weak inhibition of Pgp). In most such cases no preventive dosage adjustments are recommended and clinical monitoring only is advised. Lenacapavir overall characteristics thus meet the major clinical-pharmacologic expectations of this new era of antiretroviral development. A safe and truly potent antiviral drug, with a low metabolic interactive potential and a frequency of administration with the potential to be successfully employed beyond the current therapeutic indications.