Once-Yearly HIV PrEP Therapy Islatravir Shows Promising Early Clinical Results

Today, MSD announced that islatravir (formerly known as MK-8591), an innovative nucleoside reverse transcriptase translocation inhibitor (NRTTI) for the treatment of HIV infection, achieved positive results in Phase 1 clinical trials. The trial results demonstrated that the subcutaneously implanted drug-eluting implant can sustain the long-term release of islatravir, maintaining intracellular drug concentrations above the pharmacokinetic threshold for more than one year. This suggests that the drug has the potential to become a once-yearly pre-exposure prophylaxis (PrEP) regimen for HIV prevention.

AIDS was once a fatal disease that struck fear into people’s hearts. However, with the advent of “cocktail therapy,” AIDS has become a chronic condition manageable with medication. Nevertheless, in some countries, the incidence of AIDS remains high. Pre-exposure prophylaxis (PrEP) aims to provide preventive treatment to individuals at risk of HIV-1 infection, thereby reducing their risk of contracting HIV-1. However, current PrEP regimens require high-risk individuals to take preventive medication daily, and poor adherence to this regimen increases their risk of infection.

Islatravir is an innovative nucleoside reverse transcriptase translocation inhibitor (NRTTI) developed by MSD. Preclinical studies have demonstrated that it inhibits the function of HIV reverse transcriptase through multiple mechanisms, with a mode of action distinct from currently approved anti-HIV therapies and traditional nucleoside reverse transcriptase inhibitors (NRTIs). MSD is currently evaluating its efficacy in multiple clinical trials, both as a monotherapy for pre-exposure prophylaxis (PrEP) and in combination with other antiviral agents for the treatment of HIV infection.

▲Islatravir (MK-8591) can be used for long-term treatment or pre-exposure prophylaxis of HIV-1 (Image source: MSD official website)

In this Phase 1 clinical trial, islatravir was loaded into a matchstick-sized polymer drug-eluting implant. The implant was subcutaneously inserted into the upper arm of healthy volunteers and removed after 12 weeks.

Through the detection of monocytes in peripheral blood, studies have found that implants can maintain intracellular islatravir concentrations above pharmacokinetic thresholds for up to 12 weeks. Subsequent simulation studies indicated that implants containing 62 milligrams of islatravir could sustain drug concentrations for 12 months or longer. These preliminary findings suggest that this approach may offer a PrEP regimen requiring administration only once per year.

“These proof-of-concept trial results are highly encouraging,” said Dr. Roy Baynes, Senior Vice President of Merck Research Laboratories, Head of Global Clinical Development, and Chief Medical Officer. “Merck recognizes that individuals at risk of HIV-1 infection need multiple options. Leveraging our expertise in drug delivery, we are committed to realizing the potential of islatravir as pre-exposure prophylaxis for HIV-1.”

References:

[1] Merck Presents Early Evidence on Extended Delivery of Investigational Anti-HIV-1 Agent Islatravir (MK-8591) via Subdermal Implant. Retrieved July 23, 2019, from https://www.mrknewsroom.com/news-release/research-and-development-news/merck-presents-early-evidence-extended-delivery-investiga

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