Merck’s Novel Antibody MK-2214 Receives FDA Fast-Track Designation Following Phase 1 Results

In recent news, Merck’s MK-2214, a novel antibody targeting phosphorylated serine 413 (pS413), has earned FDA fast-track designation following positive safety, tolerability, and serum pharmacokinetic results from three separate phase 1 studies. Overall, the first in-human data for MK-2214 indicated a clean safety profile and predictable pharmacology, supporting its continued development as a potential therapy aimed at slowing the progression of Alzheimer disease (AD).^1,2

Presented at the 18th Clinical Trials on Alzheimer’s Disease Conference (CTAD), held December 1-4, in San Diego, California, Merck Pharmaceuticals reported results from 3, phase 1, randomized, double blind, placebo-controlled studies of MK-2214. In addition to assessing safety, tolerability and serum pharmacokinetics, studies 1 and 3 measured drug concentrations in cerebrospinal fluid (CSF), while study 3 evaluated free pS413 tau levels in CSF.

“Alzheimer 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 Merck Research Laboratories, said in a statement.² “We are pleased to share data showing progress in our pipeline of candidates targeting Alzheimer’s disease at CTAD 2025.”²

Led by Seth Robey, director of quantitative pharmacology and pharmacometrics at Merck Pharmaceuticals, the 3 studies included different demographics of patients, testing various dose ranges of MK-2214 and varying levels of disease progression. Studies 1 and 2 assessed the safety, tolerability and pharmacokinetics of a single ascending dose of the agent in healthy volunteers. Conversely, study 3 assessed the safety, tolerability and pharmacokinetics of a multiple ascending dose regimen in individuals with mild cognitive impairment and mild-to-moderate AD. The results from these studies helped inform an ongoing phase 2 trial of MK-2214 evaluating safety and efficacy, including its effect on certain changes in the brains of people with early AD.²

Study 1: First-In-Human Single Dose

Study 1 included 64 healthy, non-Japanese men and women aged 18-55 (mean age: 36) who received a single dose of the study medication. Of these, 36 participants received intravenous (IV) MK-2214 at doses of 10 mg (n = 6), 50 mg (n = 6), 200 mg (n = 6), 700m g (n =6), 2100 mg (n =6), or 4200 mg (n =6), and 12 received IV placebo. The remaining 16 participants were assigned to subcutaneous (SC) administration: 12 received MK-2214 at 50 mg (n = 6), or 200 mg (n = 6), and 4 received SC placebo.

Results from study 1 show that 33 of the 48 total participants (68.8%) who received MK-2214 experienced one or more adverse events (AEs), including 23 of 36 (63.9%) dosed IV (63.9%) and 10 of 12 dosed SC (93.8%). In comparison, 15 of 16 participants on placebo (93.8%) reported at least one AE. Additionally, 15 of the 48 dosed participants (31.3%) on MK-2214 experienced a drug-related AE, compared with 7 of 16 participants (43.8%) in the placebo. Furthermore, the geometric mean CSF-to-serum MK-2214 concentration percentages were 0.26% on Day 28 after a single dose of 200 mg IV and 0.31% on Day 28 after a single dose of 200 mg SC. Notably, no participant in either group discontinued treatment due to an AE.

Study 2: Single-Dose, Japanese-Based

Study 2 included 48 healthy Japanese men who received a single ascending IV dose, divided in two age groups: younger participants aged 18-55 (mean age: 42; n = 36), and older participants aged 56-75 (mean age: 62; n = 12). Among the younger participants, 27 received MK-2214 at doses of 700 mg (n = 9), 2100 mg (n = 9), or 4200 mg (n = 9), while all the older participants (n = 9) received 4200 mg. Regarding placebo, 9 younger and 3 older participants received placebo.

Findings from study 2 showed that 30.6% (n = 11) of the dosed participants across both age groups experienced one or more AE, compared with 16.7% (n = 2) of the placebo participants. Drug-related AEs were reported in 4 dosed participants (11.1%), while none occurred in the placebo group. Consistent with study 1, no participant in either group discontinued treatment due to an AE.

Study 3: Cognitively Impaired, Multiple Dose

Study 3 included 34 men and women aged 50-80 (mean age: 71) with mild to moderate cognitive impairment, who received multiple ascending IV doses of MK-2214-1 dose per month for 3 months. Of these, 25 participants received MK-2214, with doses ranging from 4 mg (n = 6) to 500 mg (n = 6), and intermediate doses of 20 mg (n = 7) and 100 mg (n = 6). In addition, placebo was administered to 9 participants.

Results from study 3 showed that 19 of the 25 dosed participants (76%) experienced one or more AE, compared with 7 of 9 placebo participants (77.8%). Drug-related AE was reported in 6 dosed participants (24%) and 1 placebo participant (11.1%). Unlike the previous two studies, 1 participant in the placebo group discontinued treatment due to an AE.

Pharmacokinetic analysis revealed that geometric mean CSF to serum MK-2214 concentration percentages ranged from 0.29% to 0.45% on Day 28 after single IV doses from 4 mg to 500 mg. Notably, reductions in CSF pS413 tau concentrations were consistent with high potency and near-saturating target engagement.

These results were gathered prior to the ongoing randomized, placebo-controlled, double-blind, parallel-group phase 2 (NCT07033494) study testing the safety and efficacy of MK-2214. Participants (n = 340) aged 50 to 85 with early AD were given an IV dose of MK-2214 or placebo.

The primary endpoints of the phase 2 trial aims to measure the change from baseline in tau PET standardized Uptake Value Ratio (SUVr), the number of participants who expirence one or more AEs, and the number of participants who discontinue treatment due to AE. The estimated completion date of phase 2 is April, 2029.

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REFERENCES
1. Robey S, Kurtz J, Cerchio K, et al. Phase 1 Studies of MK-2214, a Novel Antibody Targeting pS413 Tau, for the Treatment of Alzheimer’s Disease. Presented at: Clinical Trials on Alzheimer’s Disease Conference (CTAD); December 1-4; San Diego, California
2. Merck Showcases Data for Alzheimer’s Disease Candidates MK-2214 and MK-1167 at CTAD 2025. Merck Pharmaceuticals. News Release. December 1, 2025. Accessed December 3, 2025. https://www.merck.com/news/merck-showcases-data-for-alzheimers-disease-candidates-mk-2214-and-mk-1167-at-ctad-2025/