Eisai, Biogen: Phase 2 Alzheimer’s med safe, well tolerated

Eisai (ESALY) and Biogen (BIIB) announced that elenbecestat was generally safe and well tolerated in a Phase II clinical study of the oral BACE inhibitor elenbecestat conducted in the United States, and the results demonstrated a statistically significant difference in amyloid beta levels in the brain measured by amyloid-PET. A numerical slowing of decline in functional clinical scales of a potentially clinically important difference was also observed, although this effect was not statistically significant. This study, a Phase II study of 70 patients, is the first study of a BACE inhibitor to show a statistically significant difference in amyloid beta in the brain while also suggesting a delay of clinical symptom decline in exploratory endpoints.Study 202 is a multicenter, randomized, double-blind, placebo- controlled parallel-group 18-month Phase II clinical study in patients with mild cognitive impairment due to Alzheimer’s disease, or mild to moderate dementia due to Alzheimer’s disease with confirmed amyloid pathology by PET screening. Seventy patients were randomized to four treatment arms receiving elenbecestat or placebo daily. During the study period, more than half the patients in the elenbecestat 5 mg and 15 mg arms were switched to the 50 mg arm for three months or more. The 50 mg treatment arm plus the group switched to the 50 mg arm are hereafter referred to as “50 mg total arm” with a mean duration of approximately 11 months on 50 mg per day. Elenbecestat demonstrated acceptable safety and tolerability profile through 18 months of study drug administration. In the elenbecestat 50 mg total arm, the six most common adverse events observed were contact dermatitis, upper respiratory infection, headache, diarrhea, fall, and dermatitis. No serious adverse reactions suggestive of hepatic toxicity were observed in this study. In addition to the safety objectives, the study assessed Abeta in the brain at 18 months as measured by amyloid PET as well as efficacy in terms of clinical symptoms, which were exploratory objectives in this study. The elenbecestat 50 mg total arm demonstrated a statistically significant difference in Abeta levels in the brain as measured by amyloid PET compared with placebo This is the first time in which a significant effect in Abeta in the brain using a BACE inhibitor was confirmed in a clinical study of patients with mild cognitive impairment through moderate Alzheimer’s dementia. CDR-SB was an exploratory endpoint to assess efficacy in terms of clinical symptoms. The study showed numerically less decline in CDR-SB for the elenbecestat 50 mg total arm as compared to placebo of a potentially clinically important difference, which was not statistically significant. Further, a similar magnitude and direction of differential in decline was observed in a post-hoc analysis of ADCOMS, Eisai’s newly developed assessment scale in the elenbecestat 50 mg total arm as compared to placebo. The study was not powered to show statistical significance compared to placebo on clinical symptoms.

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