Monday, Mar 8, 2021: 11:30 AM
Virtual CROI 2021
Late Breaking Abstract
Randolph P. Matthews1, Xiaowei Zang1, Stephanie Barrett1, Adrian Goodey1, Tycho Heimbach1, Vanessa L. Weissler1, Carlien Leyssens1, Tom Reynders1, Ryan Vargo1, Yang Liu1, Robert Schwab2, Sylvie Rottey3, Michael N. Robertson1, Selwyn A. Stoch1, Marian Iwamoto1
1Merck & Co, Inc, Kenilworth, NJ, USA, 2Celerion, Lincoln, NE, USA, 3Ghent University Hospital, Ghent, Belgium
Preexposure prophylaxis (PrEP) with antiretroviral drugs has demonstrated efficacy in reducing new HIV infections, although efficacy is tightly linked to good adherence, especially in women. Islatravir (MK-8591) is a nucleoside reverse transcriptase translocation inhibitor with high potency and long t1/2, currently in development for PrEP as an oral monthly pill. In addition, prototype islatravir implants (containing only polymer and islatravir) have demonstrated the potential for yearly administration for PrEP.
Radiopaque next-generation islatravir-eluting implants were studied preclinically to establish general tolerability and assess pharmacokinetics (PK) of islatravir parent and active islatravir-TP (triphosphate). These data, along with data from an SIV challenge study and from previous Phase 1 trials, formed the basis for establishing a threshold islatravir-TP concentration of 0.05 pmol/million cells in PBMCs. In this double-blind placebo-controlled multicenter Phase 1 trial, a single islatravir-eluting (48 mg, 52 mg or 56 mg) or placebo implant was placed in participants at low risk of HIV infection for 12 weeks. Safety and tolerability, as well as PK for islatravir parent and islatravir-TP from plasma and PBMCs, was collected throughout placement and for 8 weeks post removal.
Implants were generally well tolerated, and there was no clear dose-dependent difference in implant-related adverse events (Table 1A). Active islatravir-TP levels were above target for all implants throughout implant placement (Table 1B). Data from this trial and from in vitro assessments of the ISL implants suggest that implants of >52 mg will achieve mean ISL-TP concentrations above the PK threshold at 52 weeks.
Next-generation radiopaque islatravir-eluting implants provide drug release projected to be sufficient for HIV prophylaxis for at least one year. Islatravir-eluting implants appear to be well tolerated, and the results from this trial support further study of these implants in a larger, longer Phase 2 trial. A PrEP implant could provide an attractive option for individuals in whom adherence to a daily PrEP regimen is challenging.
(G) Clinical Pharmacology in Adults
Does this abstract include any aspects of research on SARS-CoV-2 or COVID-19?
Prior Presentation or Publication: In general, CROI does not accept work that has been previously published or publicly presented. Abstract text that is under copyright by a publication or another conference should not be submitted verbatim to CROI. Consideration may be given to a previously presented submission if meaningful newer data or different analyses are included or if the prior presentation was to a conference not focused on HIV- or SARS-CoV-2-related topics. Have your study data or abstract information been published, submitted for publication where publication is anticipated on or before the start of the CROI where you will present, or presented at any other major national or international scientific or medical HIV-related conferences (ie, generally 400 or more attendees)?