|The following article is part of conference coverage from the 2018 Alzheimer’s Association International Conference in Chicago, Illinois. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AAIC 2018.|
CHICAGO — Low-dose gantenerumab administered over104 weeks appears to act on cerebrospinal fluid (CSF) biomarkers as well as Alzheimer disease pathology in patients with mild Alzheimer disease, according to findings from the Marguerite RoAD study presented at the 2018 Alzheimer’s Association International Conference, July 22-26, 2018 in Chicago, Illinois.
In a previous study, SCarlet RoAD, gantenerumab had demonstrated a dose-dependent effect on CSF tau species. The current phase 3, randomized, double-blind, placebo-controlled, safety and efficacy study (N=389) evaluated the impact of low-dose gantenerumab on amyloid and tau biomarkers in CSF. Study patients with mild Alzheimer disease were randomly assigned to subcutaneous (SC) injections of gantenerumab 105 mg (up-titrated to 225 mg) or placebo. At the time of screening, patients were required to have evidence of amyloid pathology (CSF Aβ1–42 ≤700 pg/mL); dose up-titration occurred at week 28 if there were no signifiant amyloid-related imaging abnormalities.
Patients’ CSF samples were obtained at screening, optionally at week 52, and at week 104 or early termination. The data showed a median increase of Aβ1–42 among gantenerumab-treated patients but a decrease in the placebo arm (+7.2% vs -2.2%; P =.26) at week 104. For Aβ1–40, a similar decrease was seen in both placebo and gantenerumab arms at week 52 (-5.7 vs -6.2; P =.90).
A larger decrease in tTau (-6.2 vs +3.9; P =.06) and pTau (-16.3 vs 1.40; P =.01) levels were observed in the gantenerumab arm vs placebo arm at week 104. Overall, study authors identified pTau as a biomarker that showed a statistically significant difference between the 2 compared arms.
The findings “suggest gantenerumab has an effect on CSF biomarkers of AD pathology after 104 weeks of low-dose treatment. These percentage changes in biomarkers were consistent with those in [SCarlet RoAD],” stated lead author Nicola Voyle, PhD, from Roche Products Ltd, Welwyn Garden City, United Kingdom.
Gantenerumab, a fully human anti-Aβ monoclonal antibody, is thought to exert its effect by binding and helping to remove aggregated Aβ. Higher doses will be investigated in the company’s ongoing phase 3 development program.
Disclosures: This study was funded by Roche and Genentech.
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Voyle N, Abi-Saab D, Klein G, et al. The effect of low doses of gantenerumab on amyloid and tau biomarkers in cerebrospinal fluid (CSF) in the Marguerite Road study. Presented at: 2018 Alzheimer’s Association International Conference. July 22-26, 2018; Chicago, IL. Oral presentation #O1-09-02