Favorable Profile Data On MK-2214 for Treatment of Alzheimer Disease

Merck pharmaceutical company shared new data on MK-2214 for treatment of Alzheimer disease at the 2025 Clinical Trials on Alzheimer’s Disease (CTAD) conference, December 1-4 in San Diego, California. Phase 1 trials on the drug showed a favorable profile to slow the progression of Alzheimer disease.¹

“Alzheimer’s disease remains one of the greatest neurological challenges of our time and yet new insights are providing important new paths to evaluate potential new therapeutic approaches,” said Mike Egan, MD, vice president of neuroscience, global clinical development, Merck Research Laboratories, in a press release. “We are pleased to share data showing progress in our pipeline of candidates targeting Alzheimer’s disease at CTAD 2025,” he added.²

The phase 1 trial consisted of 3 randomized, double-blind, placebo-controlled studies. Participants were assessed for follow up between 139 (study 1) and 239 days (studies 2 and 3) after medication dosing.¹ Studies 1 and 3 assessed concentration of the drug in participants cerebrospinal fluid, along with study 3 assessing effects on free pS413 tau levels in cerebrospinal fluid. Study 1 was the first-in-human single dose study for MK-2214, with 64 healthy participants aged 18 to 55. Both intravenous (IV) and subcutaneous administration were used, with 10, 50, 200, 700, 2100, or 4200 mg single doses for IV and 50 or 200 mg single doses for the subcutaneous route. The second study evaluated 48 healthy Japanese men in both younger (18 to 55) and older (56 to 75) groups with IV administration of 700, 2100, or 4200 mg single dose. To evaluate cognitively impaired patients, study 3 included 34 individuals aged 50 to 80 with multiple ascending IV doses (1 dose per month for 3 months) of 4, 20, 100, and 50 mg.

The drug was found to have a lengthy half-life of around 80 days, as estimated across all 3 studies. Single dose administration in healthy participants and multiple doses in participants with mild to moderate cognitive impairment showed good tolerability at doses which produced near-saturated binding of free pS413 tau. The bioavailability of the subcutaneous injection vs IV administration in study 1 was 0.63 across the 50 and 200 mg doses. In study 3, geometric mean CSF-to-serum MK-2214 concentrations ranged from 0.29% to 0.45% 28 days after single IV doses of 4 to 500 mg. Study 3 also found reductions in CSF pS413 tau concentrations to be consistent with high potency and near-saturating levels of target engagement.

MK-2214 was found to be generally well-tolerated at all dose levels tested in the trial.¹ No serious drug-related adverse events or pattern of drug-related events occurred, and there were no dose limiting tolerability issues. The most common adverse events were headache (studies 1 and 3) and orthostatic hypotension (study 2).

MK-2214 is an investigational novel antibody-targeting phosphorylated serine 413 (pS413) tau which intends to target abnormal accumulation and aggregation of tau in the brain, a commonly acknowledged aspect of Alzheimer disease.²

The drug has been granted Fast Track designation by the US Food and Drug Administration and has an ongoing phase 2 trial evaluating MK-2214 for slowing progression of tau spreading in individuals with early Alzheimer disease.^1,3

References

1. Robey S, Kurz J, Cerchio KA, et al. Phase 1 studies of MK-2214, a novel antibody targeting pS413 tau, for the treatment of Alzheimer’s disease. Poster presented at: Clinical Trials for Alzheimer’s Disease; December 1-4, 2025; San Diego, California.

2. Merck showcases data for Alzheimer’s disease candidates MK-2214 and MK-1167 at CTAD 2025. Press release. December 1, 2025. Accessed December 4, 2025. https://www.merck.com/news/merck-showcases-data-for-alzheimers-disease-candidates-mk-2214-and-mk-1167-at-ctad-2025/

3. Jeffries, E. Merck Alzheimer’s drug granted FDA fast track designation. December 1, 2025. Accessed December 4, 2025. https://www.beckershospitalreview.com/pharmacy/merck-alzheimers-drug-granted-fda-fast-track-designation/