AC Immune SA announced that its partners presented the first quantitative data from the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) Colombia Trial during a Focused Topic Session at the Alzheimer's Association International Conference (AAIC). The study evaluated the potential of the anti-amyloid beta antibody crenezumab to slow or prevent Alzheimer's disease in cognitively unimpaired people who carry a specific genetic mutation which causes early-onset Alzheimer's disease. As previously reported on June 16, 2022, the trial did not meet its co-primary endpoints (API ADAD composite cognitive total score and the Free and Cued Selective Reminding Test Cueing Index).

Numerical differences favoring crenezumab over placebo were observed across both of these co-primary endpoints; statistical significance was not reached. Additional clinical and biomarker measures also showed numerical differences favoring crenezumab over placebo that did not reach statistical significance. Clinical endpoints showed the following relative changes in annualized scores compared to placebo, in all cases favoring crenezumab though in all cases not statistically significant: Cognitive test scores: API ADAD composite 22.9% (p=0.43); FCSRT 19.9% (p=0.16); RBANS total score 43.8% (p=0.55); Clinical/function: Time to MCI/dementia due to AD 20.8% (p=0.48); time to non-Zero in CDR-GS 8.1% (p=0.76); CDR Sum of Boxes 8.8% (p=0.64).

Biomarker results also favored crenezumab with the following relative changes compared to placebo, all favoring crenezumab though not statistically significant: PET measures: Aß PET SUVR 3.6% (p=0.69); Tau-PET SUVR 51.1% (p=0.20); FDG PET SUVR 18.1% (p=0.25); CSF measures: t-tau 28.7% (p=0.53); p-tau-181 37.4% (p=0.28); NfL 18.2% (p=0.46). The API ADAD trial enrolled 252 people who are members of the world's larger extended family with ADAD in Colombia. Two-thirds of participants carried the Presenilin 1 E280A mutation which typically causes cognitive impairment due to Alzheimer's disease around age 44.

Approximately half of enrolled mutation carriers were negative for amyloid beta at enrolment. Participants were randomized to receive crenezumab or placebo for a planned duration of five to eight years. During the trial, the dose of crenezumab was increased more than seven-fold as knowledge about potential treatment approaches for Alzheimer's disease evolved.

The average age of mutation carriers enrolled in the trial was 37. Limitations of the API ADAD study noted in the AAIC presentation included limited statistical power to determine whether treatment with crenezumab at the optimal dose, which was received by most subjects for only about two out of five years, would have a clinical benefit. Demographic and baseline data indicate the study's lower-than-expected statistical power may have been due to a confluence of factors, including a study population that was on average younger and at an earlier preclinical Alzheimer's disease stage than expected.