Islatravir: Investigating Long-Term Treatment Options for PrEP

Currently, there are 2 Food and Drug Administration (FDA) approved pre-exposure prophylaxis (PrEP) therapies, which are both daily oral pills. There are studies underway looking at various dosing schedules and different forms of PrEP including pills, injectables, and implants. For the latter, Merck is studying its islatravir (MK-8591) for a potential PrEP indication and recently announced their phase 1 results.

The phase 1 study looked at the pharmacokinetics (PK) of the implant for 3 months, but the goal is eventually to have an implant work for a full year according to Randy Matthews, PhD, MD, senior principal scientist, Merck said.

Islatravir a highly potent nucleoside reverse transcriptase translocation inhibitor (NRTTI) with a long intracellular half-life, is currently in development to treat and prevent HIV. The therapy works by rapidly converting to its active triphosphate (TP) form, islatravir-TP, within targeted cells. Islatravir-TP inhibits reverse transcriptase to suppress HIV replication. In addition to its long intracellular half-life, islatravir has high antiviral potency against HIV and its drug-resistant variants.

For the phase 1 study, investigators conducted a randomized, double-blind, placebo-controlled trial in adults without HIV. There were 16 participants in 2 cohorts. In what they called Panel A, 6 participants received the implant with 54 mg dose of islatravir, and 2 received a placebo. All the participants were white males with an average age 35.9 years. In Panel B, 6 received the 62mg dose of islatravir and 2 received a placebo. This cohort had 6 males, and 2 females with an average age of 36.8 years. All the participants were white in this cohort.

They had the implants in for 12 weeks and they were followed up to 4 weeks afterwards.

"In the high dose implants we did see the concentrations that we wanted in everybody, and the mean concentrations for both the low dose and the high dose implant were above the PK threshold,” Matthews said.

Contagion spoke to Matthews on the therapy’s mechanism of action, the study’s results, implant placement, and potential benefits including it possibly being a yearly administration.