Journal Article

DZNE-2026-00253

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Safety, tolerability and biomarker results of bepranemab in participants with progressive supranuclear palsy: a randomised, multicentre, double-blind, placebo-controlled, phase 1b trial.

Höglinger, G. (First author)DZNE* ; Vandenberghe, W. ; Woitalla, D. ; Corvol, J.-C. ; Van Tricht, H. ; Ewen, C. ; Van Den Steen, B. ; Rebollo Mesa, I. ; Germani, M. ; Garric, E. ; Arnould, T. ; Jose, J. ; Strong, N. ; De Bruyn, S. ; Buchanan, T. J.

2026
BMJ Publishing Group London

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Please use a persistent id in citations: doi:10.1136/bmjno-2025-001396

Abstract: Preclinical evidence suggests targeting the mid-region of tau as a viable therapeutic strategy in diseases such as progressive supranuclear palsy (PSP): a rare, fatal, neurodegenerative tauopathy with no currently approved treatments. Bepranemab is a recombinant, humanised, full-length immunoglobulin G4 monoclonal antibody binding to a mid-region tau epitope. We assessed safety, tolerability and pharmacokinetics of bepranemab in participants with PSP.PSP003 (NCT04185415), a multicentre, double-blind, placebo-controlled, phase 1b study, recruited participants in hospital settings across 13 centres. Participants (aged ≥40 years) met Movement Disorder Society-PSP criteria for possible/probable PSP, could walk ≥5 steps with minimal/no assistance and were stable on treatment for ≥2 weeks prior to baseline. Participants were randomised 3:1 to receive intravenous bepranemab (90 mg/kg) or placebo every 4 weeks for 52 weeks. Primary endpoint: incidence of treatment-emergent adverse events (TEAEs) from baseline to last visit.Twenty-five participants were enrolled (male: 44%; bepranemab n=18, placebo n=7). Seventeen (94.4%) in the bepranemab group reported ≥1 TEAE (five participants; ten investigational medicinal product (IMP)-related TEAEs), versus placebo (n=7; 100%). In the bepranemab and placebo groups, respectively, three participants (16.7%) and one participant (14.3%) discontinued due to TEAEs. Incidence of IMP-related TEAEs and severe TEAEs was similar between groups; no deaths were reported. Reduction (80.41%) in mean free tau cerebrospinal fluid levels was observed in the bepranemab group.Multiple doses of bepranemab 90 mg/kg were well tolerated with an acceptable safety profile in participants with PSP. High target occupancy was observed.

Keyword(s): ALZHEIMER'S DISEASE ; CLINICAL NEUROLOGY ; RANDOMISED TRIALS ; SUPRANUCLEAR PALSY

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2026

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Emerging Sources Citation Index ; Fees ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Web of Science Core Collection

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