Japanese participant data from three gantenerumab trials in early Alzheimer's disease.

INTRODUCTION

Gantenerumab was investigated in Japanese participants with mild cognitive impairment due to Alzheimer's disease (AD) or mild AD in two global phase 3 trials (GRADUATE I/II), and a phase 2 trial in Japan (JP40959).

METHODS

Of 1965 participants randomized in GRADUATE I/II (global-GRADUATE), 132 participants were enrolled from Japan (Japanese-GRADUATE) and 67 Japanese participants were randomized 2:1:1 to high-, low-dose gantenerumab, and placebo in JP40959.

RESULTS

Slowing of cognitive and functional decline, and amyloid reduction in gantenerumab group compared to placebo group were greater in Japanese-GRADUATE than in the global-GRADUATE and JP40959. Plasma gantenerumab concentrations in the Japanese-GRADUATE were slightly higher than in the global-GRADUATE and comparable to JP40959. Gantenerumab was well tolerated in the Japanese-GRADUATE and JP40959, matching the safety profile of the global-GRADUATE.

DISCUSSION

Differences in results across the populations studied could be related to imbalances in baseline body weight, amyloid load, and disease severity.

TRIAL REGISTRATION NUMBER

ClinicalTrials.gov ID: NCT03444870, NCT03443973; Japan Registry for Clinical Trials ID: jRCT2080224569.

HIGHLIGHTS

Gantenerumab was evaluated in Japanese participants with Alzheimer's disease (AD) in two global phase 3 trials and a phase 2 trial in Japan. Relative reduction in Clinical Dementia Rating Sum of Boxes (CDR-SB) deterioration favored gantenerumab in Japanese-GRADUATE (42%) more than in global-GRADUATE (9%) and JP40959 (-24%). Amyloid reduction in Japanese-GRADUATE was greater than in global-GRADUATE and JP40959. Overall, 72.7% and 27.5% of Japanese- and global-GRADUATE, respectively, achieved an amyloid-negative status. Cognitive and functional decline, and amyloid reduction could be related to baseline body weight and disease severity.