Aducanumab 36-month data from PRIME: a randomized, double-blind, placebo-controlled Phase 1b study in patients with prodromal or mild Alzheimer’s disease (S2.004)

Objective: We report 36-month data for fixed-dose cohorts, including 12 months from the placebo-controlled period and 24 months from the long-term extension (LTE). Background: PRIME is an ongoing Phase 1b study evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics of aducanumab in patients with prodromal or mild AD. Design/Methods: Patients in PRIME, aged 50–90 years, had a positive florbetapir PET scan, and met clinical criteria for prodromal/mild AD. During the double-blind, placebo-controlled phase, patients were randomized to fixed doses of aducanumab stratified by ApoE ɛ4 status and received aducanumab or placebo q4w for 52 weeks. In the LTE, all patients received aducanumab 3, 6, or 10 mg/kg fixed or titrated. With the exception of safety, all LTE endpoints, including measurement of Aβ reduction by PET and changes in clinical endpoints, were exploratory. Results: In patients treated up to 36 months, amyloid plaque levels continued to decrease in a dose- and time-dependent manner, with levels in the 10 mg/kg fixed-dose group reaching and remaining below a quantitative cut-point discriminating a positive/negative scan. 1 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 for patients continuing aducanumab over 36 months. No new patients who continued at the same dose of aducanumab experienced ARIA-E. ARIA-E incidence at 36 months in patients switching from placebo to aducanumab was consistent with that reported on active treatment in the placebo-controlled phase. Conclusions: In patients from fixed-dose cohorts who completed the first two years of the LTE, amyloid plaque levels continued to decrease in a dose- and time-dependent manner and analyses of the clinical endpoints suggest a continued clinical benefit. These data support further investigation of aducanumab in the ENGAGE and EMERGE Phase 3 trials. Study Supported by: Biogen Disclosure: Dr. Budd Haeberlein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Gheuens has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Chen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. O9Gorman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Von Rosenstiel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Chiao has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Wang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen; Cytel. Dr. Von Hehn has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Skordos has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Hock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Neurimmune. Dr. Nitsch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Neurimmune. Dr. Sandrock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Sandrock holds stock and/or stock options in Holds stock/options in Biogen.