Biogen has announced results from a recently conducted analysis of the long-term extension (LTE) of its ongoing phase 1b study of aducanumab, the company’s investigational treatment for early Alzheimer’s disease.
The updated analyses include data from the placebo-controlled period and LTE for patients treated with aducanumab up to 24 months in the titration cohort and up to 36 months in the fixed-dose cohorts. The results are consistent with previously reported analyses from this ongoing phase 1b study and support the design of the ongoing phase 3 studies of aducanumab for early Alzheimer’s disease.
The phase 1b is a randomized, double-blind, placebo-controlled, multiple-dose study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical effects of aducanumab in patients with prodromal or mild Alzheimer’s disease. The study includes fixed dosing at 1, 3, 6 and 10 mg/kg as well as an arm with a titration regimen.
Phase 1b long-term extension: Patients who completed the 54-week, placebo-controlled period of the Phase 1b study had the option to continue in the LTE.
The new analyses include 143 patients who remained in the LTE. The LTE cohorts are small populations:
Patients (n=18) initially randomized to the aducanumab titration regimen in the 12-month placebo-controlled period and treated up to 24 months
Patients (n=69) initially randomized to aducanumab 3, 6 or 10 mg/kg and treated up to 36 months
Patients (n=48) who were randomized to placebo or aducanumab 1 mg/kg in the placebo-controlled period who were switched to aducanumab 3 mg/kg or to a 3-6 mg/kg titration regimen in the LTE and treated up to 24 months
Patients (n=8) who were randomized to placebo in the placebo-controlled period who were switched to aducanumab 1-3-6-10 mg/kg titration regimen in the LTE and treated up to 12 months
In the phase 1b LTE, the most commonly reported adverse events were headache, fall and amyloid-related imaging abnormalities (ARIA). Of the 185 patients dosed with aducanumab in the Phase 1b study, 46 patients experienced ARIA-E (edema). There were no new cases of ARIA-E in patients who continued on the same dose of aducanumab. The incidence of ARIA-E in patients switching from placebo to aducanumab was consistent with the incidence reported in the placebo-controlled portion of the Phase 1b study. Six patients experienced more than one episode of ARIA-E. These recurrent events were consistent with other ARIA events reported to date; they were typically asymptomatic, and most patients continued in the study.
In patients treated up to 24 months in the titration cohort, amyloid plaque reduction as measured by positron emission tomography (PET) was consistent with the dose- and time-dependent results observed in the fixed-dose cohorts. Analyses of exploratory clinical endpoints, Clinical Dementia Rating sum of boxes (CDR-SB) and the Mini-Mental State Examination (MMSE), were consistent with the results from the fixed-dose cohorts and suggest a continued benefit on the rate of clinical decline during the second year of treatment.
In patients treated up to 36 months, amyloid plaque as measured by PET continued to decrease in a dose- and time-dependent manner, with amyloid plaque levels in the 10 mg/kg fixed-dose cohort reaching and remaining at a level considered below the quantitative cut-point that discriminates between a positive and negative scan1. At 36 months, analyses of exploratory clinical endpoints CDR-SB and the MMSE suggest a continued benefit on the rate of clinical decline during the third year of treatment.
Biogen plans to share more data from these analyses at an upcoming medical congress.
Aducanumab is currently being evaluated in two global phase 3 studies, ENGAGE and EMERGE, which are designed to evaluate its safety and efficacy in slowing cognitive impairment and the progression of disability in people with early Alzheimer’s disease.