PrEP Implant Phase 1 Results are Reported

Merck reported today that a phase 1 trial of its islatravir (formerly MK-8591) subdermal implant for prevention of HIV-1 infection demonstrated it achieved active drug concentrations above the pre-specified PK threshold at 12 weeks across the three doses of islatravir studied (48 mg, 52 mg and 56 mg).

Islatravir is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI).

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.

The data was presented during the Conference on Retroviruses and Opportunistic Infections (CROI) 2021 virtual sessions.

Radiopaque next-generation islatravir-eluting implants were studied preclinically to establish general tolerability and PK of islatravir parent and of the active islatravir-TP (triphosphate). These data, along with data from an SIV challenge study and from previous phase 1 trials, formed the basis of models for establishing a threshold islatravir-TP concentration of 0.05 pmol/106 cells in PBMCs.

Merck also projected the implant will provide drug concentrations likely above threshold for one year at the 56 mg dose, and the company is planning to initiate a phase 2 trial to further explore the potential of a subdermal implant containing islatravir for PrEP for up to 12 months.

Trial investigator Randolph Matthews, MD, PhD, senior principal scientist, Merck, explained that islatravir is unique from other NRTTIs in two distinct ways.

“Whereas a traditional NRTTI works by immediate chain termination, islatravir [works] both with delayed chain termination and immediate chain termination…this makes the compound very potent,” Matthews said.

In addition, the therapy has about 190 hour half-life, according to Matthews.

“The high potency and the long half-life make it very attractive options for long-term delivery through an implant,” Matthews stated.

The therapy is being studied for a number of applications, Matthews explained. Islatravir is being studied for pre-exposure prophylaxis (PrEP) of HIV-1 infection as a single agent across a variety of formulations, including the IMPOWER clinical trials evaluating an oral once-monthly regimen. It is also under evaluation in clinical trials for the treatment of HIV in combination with other antiretrovirals, including the ILLUMINATE clinical trials program for once-daily treatment.

Contagion spoke to Matthews about the phase 1 trial, the different ways it is being studied, and the implant the company is using for its trials.