Cambridge, Mass.-based Biogen and Tokyo, Japan-based Eisai Co. announced results from an analysis of their ongoing long-term extension (LTE) Phase Ib trial of aducanumab for Alzheimer’s disease.
Cambridge, Mass.-based Biogen and Tokyo, Japan-based Eisai announced results from an analysis of their ongoing long-term extension (LTE) Phase Ib trial of aducanumab for Alzheimer’s disease.
The current updated analysis included data from the placebo-controlled period and LTE for patients treated with the drug up to 36 months in the titration cohort and up to 48 months in the fix-dose cohorts. The companies report the data are generally consistent with previous interim data reports and there were no changes to the risk-benefit profile of the drug.
Aducanumab (BIIB037) is being studied in early Alzheimer’s disease. It is a human recombinant monoclonal antibody (mAb) made up of a de-identified library of B cells collected from healthy elderly patients with no signs of cognitive impairment or cognitively impaired elderly subjects with unusually slow cognitive decline. They were collected using Neurimmune’s technology platform, Reverse Translational Medicine (RTM). Biogen licensed aducanumab from Neurimmune. Since October 22, 2017, Biogen and Eisai have been collaborating on developing and commercializing aducanumab.
The Phase Ib clinical trial is a randomized, double-blind, placebo-controlled, multiple-dose trial to evaluate the safety tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical effects of aducanumab in patients with prodromal AD or mild AD dementia. There are fixed doses of 1, 3, 6 and 10 mg/kg in addition to an arm with a titration regimen where patients are given gradually increasing doses of aducanumab until they hit 10 mg/kg.
In the Phase Ib trial, 196 patients received either aducanumab or placebo. Of those, 143 patients entered LTE. The LTE cohorts were divided across six dosing arms, which included placebo switchers, 1 mg/kg switchers to 3 mg/kg, fixed doses of 3, 6 and 10 mg/kg, and titration. There were expected discontinuations, which means there were fewer patient numbers in the new analyses.
Levels of amyloid beta plaque were measured by positron emission tomography (PET). Patients showed a decrease in a dose and time-dependent matter of amyloid levels from the titration cohort at 36 months and fixed-dose cohorts at 48 months.
There were exploratory clinical endpoints evaluated, including Clinical Dementia Rating Sum of Boxes (CDR-SB) and the Mini-Mental State Examination (MMSE). These data suggested a continued befit on the rate of clinical decline over 36 and 48 months.
The companies stated, “Of the 185 patients dosed with aducanumab in the Phase Ib study, 46 patients experienced amyloid imaging abnormalities (ARIA)-E (edema). Eight patients experienced more than one episode of ARIA-E. The majority of ARIA events occurred early in the course of treatment; they were typically mild radiographically (MRI), clinically asymptomatic and resolved or stabilized within 4-12 weeks, with most patients continuing treatment. In the Phase Ib LTE, the most commonly reported adverse events were headache, fall and ARIA.”
This announcement seems to have investors and analysts pausing. In late-July, the two companies disclosed data from their BAN2401 Alzheimer’s trial, which caused Biogen shares to drop slightly, largely based on some skepticism over their actual meaning of the results, which overall appeared positive. In that trial, patients taking the highest dose of the drug showed a 30 percent decrease in cognitive decline compared to placebo. And in the patients receiving the highest dose of BAN2401, 81 percent tested negative for amyloid after 18 months of treatment. But investors and analysts focused on the details, noting that patients on low doses of BAN2401 did not matter, and in some cases did worse, than patients receiving placebo. There was also concern that the companies had also excluded patients carrying the APO4 gene, which is linked to increased risk of late-onset Alzheimer’s.
Today’s stock, so far, is remaining largely unaffected by the news. Biogen shares opened at $344.42 and are currently at $343.34. Eisai took a little harder hit. It was trading at 9,962 yen for a high on August 27 and is currently trading at 9,743 yen.
