Getting under your skin

KENILWORTH, NJ—A possible new preventative option against HIV is moving through the clinical pipeline on track, with Merck, known as MSD outside of the US and Canada, sharing results from a Phase 1 study of its investigational subdermal drug-eluting implant with potential for extended administration of islatravir for pre-exposure prophylaxis (PrEP) of HIV-1 infection. The results were shared at the 2021 Conference on Retroviruses and Opportunistic Infections (CROI 2021).

Islatravir is an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI). Merck is evaluating the compound as both a treatment for HIV-1 infection in combination with other antiretrovirals, including its ILLUMINATE clinical program with once-daily treatment, and as a single agent pre-exposure prophylaxis (PrEP) of HIV-1 infection, including Merck's IMPOWER trials of an oral, once-monthly regimen.

“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.”

This double-blind, placebo-controlled study was designed to assess the safety, tolerability, and pharmacokinetics (PK) of islatravir delivered via implant in healthy volunteers. Participants received an implant that delivered islatravir at either 48 mg (n=8), 52 mg (n=8), 56 mg (n=8), or placebo (n=12; 4 in each dose level), with the implant removed after 12 weeks and participants evaluated for another eight weeks after that.

At 12 weeks, all three doses of islatravir resulted in mean islatravir triphosphate (the active form of islatravir) concentrations above the target PK threshold (0.05 pmol/106 cells), which is the estimated lowest level needed to have an antiviral effect as monotherapy in humans based on Phase 1 and Phase 2 data. The 52 mg and 56 mg doses maintained islatravir triphosphate levels above the PK threshold in all individuals from the point of implantation until the end of the study. Sixty-seven percent of participants (24 out of 36) reported at least one implant site adverse event (AE), but all adverse events were mild or moderate and there were no discontinuations due to an AE. Merck did not identify a relationship between dose and implant site AE frequency or severity.

According to Merck, the results of this study and previous work support the potential of these implants to generate levels of islatravir triphosphate necessary to provide drug concentrations likely above the target PK threshold for at least one year. The company intends to launch a Phase 2 trial to evaluate the potential of a subdermal islatravir implant as a long-acting option for PrEP for up to 12 months.

In other recent news, Merck announced on March 4 that it had begun its tender offer for Pandion Therapeutics, a biotechnology company focused on bispecific antibody therapeutics for patients with autoimmune and inflammatory diseases and organ transplants. Merck announced its intentions to acquire Pandion on Feb. 25. The cash tender offer is being conducted through a subsidiary for all outstanding shares of Pandion common stock. Once the tender offer closes, Pandion shareholders will receive $60 for each share validly tendered and not withdrawn in the offer, without interest and less any required withholding taxes. Following the completion of the transaction, Pandion will become a Merck subsidiary.

“This acquisition builds upon Merck’s strategy to identify and secure candidates with differentiated and potentially foundational characteristics,” Dr. Dean Y. Li, president of Merck Research Laboratories, commented in February about the intended transaction. “Pandion has applied its TALON technology to develop a robust pipeline of candidates designed to re-balance the immune response with potential applications across a wide array of autoimmune diseases.”