O4‐04‐03: Additional results from a phase ii study to assess the clinical and immunological activity, safety, and tolerability of affitope® ad02 in patients with early Alzheimer's disease (AD)

AFFITOPE® AD02, is an amyloid-beta (Aβ)-targeting vaccine to elicit anti-Aβ antibodies. AD04 possesses immune enhancing properties, was originally designated as placebo, and appears to have disease-modifying activity. AD02 and AD04 were evaluated in a multicenter, parallel group, phase 2 study in early AD (late MCI and mild AD). The study enrolled 332 patients, randomly assigned to 5 groups (0.6:0.6:1:1:1): AD04 (1mg, and 2mg), 25ug AD02 (two formulations) and 75ug AD02. Patients received 6 subcutaneous injections at months 0,1,2,3,9, and 15, with final assessments at 18 months. Co-primary outcomes were Adapted ADAS-cog scale, and Adapted ADCS-ADL, plus a Composite (sum of the two scores). Primary results showed excellent tolerance with a dropout rate of 14.8%. AD04 2mg had a positive efficacy signal, and the other 4 groups had minimal effect compared to historical control. Effect sizes versus the 4 groups were from 36% to 56% slowing on primary endpoints and Right Hippocampal Volume. Large effects were seen on several other outcomes (Table 1) 48% of patients in the AD04 formulation 2 group had no decline in the composite outcome over 18 months compared to 17%-31% for the 4 groups. The MMSE 23+ patients had near stabilization on aADAS-cog and Composite over 18 months. The aADCS-ADL had similar effects for MMSE 23+ and <23, and the NPI had effects only in the MMSE<23 group, and patient QOL had a negative effect for MMSE<23. Hippocampal volume effect was better in MMSE 23+, but had an effect in the MMSE <23 group between 12 and 18 months. Effects were similar for APOEe-4 carriers and non-carriers, but were somewhat delayed for carriers. Eastern European sites had patterns similar to the MMSE<23 group and Western European sites had patterns similar to the MMSE 23+ group. Males and females had similar effects, except that aADCS-ADL and QOL patient were better in males, and NPI was better in females. Primary efficacy outcomes in this phase 2 trial were significant in favor of AD04 over AD02. Effects were better in mildest disease and Western Europe, and were seen in APOE-e4 carriers and non-carriers, and both genders.