Merck phase 1 trial for Islatravir subdermal implant to prevent HIV-1 Infection shows positive results

"We are delighted to share our early data at CROI 2021 supporting the potential for a once-yearly dosing regimen for islatravir using a subdermal implant," said Dr. Joan Butterton, vice president, global clinical development, infectious diseases, Merck Research Laboratories. "We know that PrEP can have a positive impact in curbing the spread of HIV and are looking forward to evaluating our implant further with the goal of developing new long-term options for HIV prevention."

The Phase 1 double-blind, placebo-controlled trial evaluated the safety, tolerability and PK of islatravir administered using a drug-eluting implant placed subdermally in healthy participants. People in the study received an implant containing islatravir at doses of either 48 mg (n=8), 52 mg (n=8), 56 mg (n=8) or placebo (n=12; 4 in each dose level). After 12 weeks, the implant was removed, and participants were evaluated for an additional eight weeks.

At 12 weeks, all three doses resulted in mean islatravir triphosphate (the active form of islatravir) concentrations above the target PK threshold (0.05 pmol/106 cells), the lowest level of islatravir triphosphate projected to have an antiviral effect as monotherapy in humans based on Phase 1 and Phase 2 data. The top two doses (52 mg and 56 mg) maintained islatravir triphosphate levels above the PK threshold in all individuals from implant insertion until the end of the study. The results of this study, along with previous assessments of islatravir implants, provide evidence for the potential of implants to generate levels of islatravir triphosphate projected to provide drug concentrations likely above the target PK threshold for at least one year.

In this study, 67% of (n=24/36) participants reported at least one implant site adverse event (AE). All AEs were mild or moderate in severity and there were no discontinuations due to an AE. Common AEs included erythema (3/12; 4/8; 2/8; 4/8), tenderness/pain (4/12; 2/8; 4/8; 4/8), pruritus (3/12; 5/8; 2/8; 6/8), and induration (2/12; 4/8; 4/8; 4/8) for the placebo, 48 mg, 52 mg, and 56 mg groups, respectively. The most common AE not related to the implant site was headache, affecting six individuals overall. There was no clear relationship between dose and implant site AE frequency or severity.