Drug Development

Background: evoke and evoke+ are phase 3, randomized, placebo-controlled trials currently investigating the glucagon-like peptide-1 receptor agonist semaglutide as disease-modifying therapy (DMT) in persons with early Alzheimer's disease (AD). How the evoke and evoke+ trial populations compare with other phase 3 programs for DMTs in early AD has not been described.

Method: We compare the inclusion/exclusion criteria and baseline characteristics of the evoke/evoke+ trial populations with those of Clarity AD (lecanemab) and TRAILBLAZER-ALZ-2 (donanemab): two recent phase 3 trials assessing anti-amyloid monoclonal antibodies in persons with early AD. A descriptive comparison is presented. Data cleaning of the randomized study populations of 3,806 participants in evoke/evoke+ is ongoing.

Result: From Table 1, the four trials reported a total randomized sample of 7,337 participants. The broadest age range was in Clarity AD (50-90 years vs 55-85 years in evoke/evoke+ and 60-85 years in TRAILBLAZER-ALZ-2). Race and ethnicity differed across trials, with the highest absolute number of non-White participants in evoke/evoke+ (741 vs 402 in Clarity AD and 148 in TRAILBLAZER-ALZ-2; US Hispanic participation, 23.6% in evoke/evoke+ vs 11.4% in TRAILBLAZER-ALZ-2). Cognitive inclusion criteria also differed: evoke/evoke+ and Clarity AD required deficits in episodic memory at screening (based on WMS IV-Logical Memory II test and Repeatable Battery for Neuropsychological Status Delayed Memory Index, respectively). Mild cognitive impairment and mild AD dementia in evoke/evoke+ is defined by a Clinical Dementia Rating (CDR) global score of 0.5 and 1.0, respectively. All studies required participants to demonstrate amyloid positivity. TRAILBLAZER-ALZ-2 included tau pathology by positron emission tomography (PET) at screening, with low tau pathology the most frequent reason for study exclusion. The TRAILBLAZER-ALZ-2 population had more impairment on CDR-Sum of Boxes, Mini-Mental State Examination, and CDR global.

Conclusion: All four studies targeted biologically defined early-stage AD patients but differed in cognitive inclusion criteria. TRAILBLAZER-ALZ-2 differed from evoke, evoke+ and Clarity AD in having more impaired patients and using tau PET for staging. A higher number of non-White participants were included in evoke, evoke+ and Clarity AD vs TRAILBLAZER-ALZ-2. Data for evoke and evoke+ are still subject to cleaning.