Abstract/Journal Article

DZNE-2026-00010

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Anti‐oligomeric PRI‐002 does not cause ARIA‐E in an ongoing Phase 2 trial

Peters, O. (First author)DZNE* ; Jürgens, D. ; Tischler, G. ; Brener, A. ; Bartsch, T. ; Kauselmann, G. ; Adermann, K. ; Zeiger, K. ; Lindner, K. ; Gabelich, J.-A. ; Willbold, D.

2025

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Please use a persistent id in citations: doi:10.1002/alz70861_108724

Abstract: BackgroundAmyloid related imaging abnormalities (ARIA) are a common side effect of monoclonal anti-amyloid antibodies and limit the benefit risk ratio. Here we investigate the safety and efficacy of the anti-oligomeric all-D-peptide PRI-002 in early AD. PRI-002 is an orally available, first in class compound developed to disassemble neurotoxic Aβ oligomers into non-toxic Aβ monomers. In a phase 1 B study PRI-002 has been shown to improve learning and memory function in early AD patients after 4 weeks of once-daily oral treatment and 4 weeks follow-up (Kutzsche et al., Nat. Commun. 2025).MethodPRImus-AD (NCT06182085) is an ongoing randomized, double-blind, placebo-controlled phase 2 study of PRI-002 in early symptomatic AD receiving either 300 mg, 600 mg or placebo every day for at least 48 weeks. Safety is measured by comparing adverse and serious adverse events in verum groups versus placebo. Primary efficacy outcome is CDR-SB. According to study protocol intense MRI monitoring to detect possible ARIA-E were performed during titration.Result304 patients 70.4±6.5 years on age, with a MMSE of 25.2±2.2, 155 with MCI (51.0%) and 149 (49.0%) with mild dementia were randomized. CDR-SB at baseline was 3.3±1.4 and RBANS-DMI 54.8±12.7. 208 patients have at least one APOE4 allele (68.4%). After 90 patients, irrespective of the treatment arm, had passed the first 24 weeks of treatment, the incidence of ARIA was evaluated. Within these 90 patients ARIA-E occurred in 4 (4.4%) and ARIA-H were detected in 13 (14.4%) subjects. This incidence is in line with large observational cohorts like ADNI. An unblinded DSMB reviewed the ARIA incidence in all three study arms and recommended to stop the intense ARIA monitoring for the rest of the study, since no imbalance was detected.ConclusionIn an ongoing phase 2 trial with oral PRI-002 that was designed to disassemble synaptotoxic Aβ aggregates into harmless Aβ monomers, the study drug is safe and in detail does not cause ARIA incidents Efficacy data are expected in 2026.

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Contributing Institute(s):

1. Biomarker-Assisted Early Detection of Dementias (AG Peters)

Research Program(s):

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

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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