Background

Little is known about MK-1942, a small-molecule drug Merck began to develop for treatment-resistant depression in 2021. At that time, Merck partnered with Novamind, a company focusing on clinical applications of psychedelic compounds such as those derived from psilocybin mushrooms or LSD. This prompted media speculation that MK-1942 is a related therapy (e.g., see March 2021 Psychedlic Spotlight news  and April 2021 TS news). As of February 2023, Merck had not disclosed the target of this drug.

Findings

In May 2022, Merck completed a Phase 1 drug interaction study to determine the safety of combining MK-1942 with donepezil in people with Alzheimer’s disease. Participants included 27 patients with mild to moderate dementia who were on a stable dose of donepezil. They were treated with escalating doses of MK-1942 from 8 mg twice daily for seven days, increasing to 15, 30, and up to 50 mg in seven-day increments, or placebo, in combination with donepezil up to 15 mg daily. The outcomes were the number of people with adverse events or abnormal clinical results, and pharmacokinetics.

In December 2022, the company began a Phase 2 efficacy and safety study of MK-1942 as an add-on to acetylcholinesterase inhibitor therapy in 408 people with mild to moderate Alzheimer’s dementia. Treatment was to be 12 weeks of either 5 or 15 mg twice daily, or placebo. Primary outcome is ADAS-Cog 11, plus adverse events and discontinuations. Secondary outcomes include the ADCS-CGIC and ADCS-ADL. The study ran at 20 sites in the U.S., Canada, Japan, and Korea; completion was anticipated in May 2026.

A Phase 2 trial for treatment-resistant depression, involving 140 patients at 40 locations in the U.S., was slated to finish in August 2024.

In September 2023, Merck terminated both Phase 2 trials and discontinued this program, due to potential liver toxicity (Oct 2023 Clinical Trials Arena news).

For details on MK1942 trials, see clinicaltrials.gov.