Merck phase 1 trial for Islatravir subdermal implant to prevent HIV-1 Infection shows positive results
Kenilworth: Merck, known as MSD outside the United States and Canada, has recently announced results from a Phase 1 study evaluating the safety, tolerability and pharmacokinetics (PK) of the company's investigational subdermal drug-eluting implant with potential for extended administration of islatravir for pre-exposure prophylaxis (PrEP) of HIV-1 infection.
Islatravir is an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) currently being evaluated across a variety of doses, formulations and frequencies for both the treatment of HIV-1 infection in combination with other antiretroviral agents and for the prevention of HIV-1 infection as a single agent. Study results, presented as a late-breaking oral presentation [Presentation 88] at the 2021 Conference on Retroviruses and Opportunistic Infections (CROI 2021), demonstrate that the implant 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), and is projected to provide drug concentrations likely above threshold for one year at the 56 mg dose. Based on these findings, Merck plans to initiate a Phase 2 trial to further explore the potential of a subdermal implant containing islatravir as a long-acting option for PrEP for up to 12 months.
"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.
