24-MONTH ANALYSIS FROM PRIME, A PHASE 1B STUDY IN PATIENTS WITH PRODROMAL/MILD ALZHEIMER'S DISEASE. (11th November 2018)

• Record Type: Journal Article
• Authors: von Rosenstiel, P; Gheuens, S; O'Gorman, J; Chiao, P; Hock, C; Nitsch, R; Budd Haeberlein, S; Sandrock, A
• Is Part Of: Innovation in aging. Volume 2(2018)Supplement 1
• Page Start: 135
• Page End: 135
• Publication Date: 2018-11-11
• Subjects: Aging -- Periodicals; Gerontology -- Periodicals; 612.67
• DOI: 10.1093/geroni/igy023.494
• Languages: English
• ISSNs: 2399-5300

Abstract

Abstract: PRIME is an ongoing Phase 1b study evaluating safety, tolerability, and PK/PD of aducanumab in patients (aged 50–90; positive amyloid PET scan) with prodromal/mild AD. We report 24-month data for fixed-dose and titration cohorts, including 12 months from the placebo-controlled period and 12 months from the long-term extension (LTE). During the placebo-controlled period, patients were randomized to placebo or fixed-doses of aducanumab 1, 3, 6, or 10 mg/kg, stratified by ApoE ε4 status (q4w; 52 weeks). An added cohort of ApoE ε4 carriers received aducanumab titrated to 10 mg/kg or placebo. In the LTE, all patients received aducanumab 3, 6, or 10 mg/kg fixed or titrated. Except safety, all LTE endpoints, including amyloid PET, CDR-SB, and MMSE, were exploratory. In patients treated up to 24 months from both fixed-dose and titration cohorts, amyloid plaque levels continued to decrease in a dose- and time-dependent manner. Reduced amyloid plaque levels were also observed in patients switched from placebo to aducanumab during the LTE. CDR-SB and MMSE data suggest clinical benefit in patients continuing aducanumab during the LTE. No new patients continuing at the same dose of aducanumab experienced ARIA-E during the first year of the LTE. Four patients experienced more than one ARIA-E episode over 24 months. Recurrent ARIA was consistent with other ARIA reported to date. ARIA-E incidence at 24 months in patients switching from placebo to aducanumab was consistent with that reported at 12 months in active arms. These data support further investigation of aducanumab in ENGAGE/EMERGE Phase 3 trials.