Once-Weekly Investigational MK-8507 Potent Even at Low Doses

Neil Osterweil

October 12, 2020

A single dose of MK-8507, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI), reduced HIV-1 viral loads for at least 1 week with efficacy comparable to that of other NNRTIs dosed daily for 7 days, investigators reported.

If it should receive regulatory approval, the drug's antiviral potency at doses as low as 40 mg and its pharmacokinetic profiles would make it suitable for once-weekly administration as part of a combination antiretroviral therapy regimen, according to Wendy Ankrom, PhD, and colleagues at Merck Sharp & Dohme, manufacturer of the drug.

They presented data from a phase 1b open label, proof-of-concept study during the annual HIV Glasgow drug therapy meeting, which was held virtually because of the pandemic.

HIV-1-infected males aged 22 to 56 years who were naive to antiretroviral therapy were enrolled and received a single 40 mg, 80 mg, or 600 mg oral dose of MK-8507.

Blood was collected and tested for viral load and pharmacokinetics at 14 days for 3 of 6 patients assigned to the 600 mg dose, and at 7 days for the remaining 3 patients assigned to the 600 mg dose, as well as 6 patients each assigned to the 40 and 80 mg doses.

One week after dosing, the mean viral load reduction was 1.22 log10 HIV RNA copies/mL with the 40 mg dose, 1.50 log10 copies/mL with the 80 mg dose, and 1.53 log10 copies/mL with the 600 mg dose.

The efficacy of the drug is comparable to that of other NNRTIs dosed on a daily schedule, the investigators said.

The pharmacokinetic behavior of the drug was similar to that seen in uninfected volunteers. The 7-day post-dose concentration of the drug at the 40 mg, 80 mg, and 600 mg doses were 78.1, 214, and 1400 nanomolars, respectively.

One study participant developed viral recrudescence at day 10 with the NNRTI-associated resistance variant F227C.

The participants reportedly tolerated the drug well at all dose levels, with nasopharyngitis and headache as the most common adverse events. One participant developed a diffuse large B cell lymphoma that was deemed to be unrelated to the study drug.

Following the study, all of the participants were advised to begin standard-of-care antiretroviral therapy that does not contain an NNRTI.

According to a company press release, MK-8507 is being developed for use in combination with islatravir (MK-8591), an investigational nucleoside reverse transcriptase inhibitor currently being evaluated in clinical trials for the treatment of HIV-1 infections in combination with other antiretroviral agents.

HIV Glasgow 2020 Virtual Conference: Abstract O416. October 5-8, 2020.

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