• Ole B Suhr, Martha Grogan, SilvaAna Martins daAMD0000-0002-1409-0831Unidade Corino de Andrade, Centro Hospitalar Universitário do Porto, Porto, Portugal., Chafic Karam, Pablo Garcia-Pavia, Brian Drachman, Wagner Zago, Radhika Tripuraneni, and Gene G Kinney.
• Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
• Amyloid. 2024 Oct 29: 181-8.

BackgroundThe investigational monoclonal antibody PRX004 is designed to specifically target and deplete TTR amyloid. Here, we report on the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical activity of PRX004 in patients with ATTRv amyloidosis.MethodsThis global, multicentre, phase 1 trial comprised a 3 + 3 dose-escalation phase and a long-term extension (LTE) phase (NCT03336580). In the dose-escalation phase, patients received PRX004 (0.1, 0.3, 1, 3, 10 or 30 mg/kg), administered intravenously every 28 days for 3 months. In the LTE, eligible patients could receive up to 15 additional doses. Patients who received doses of ≥3 mg/kg for ≥9 months were assessed for Global Longitudinal Strain (GLS) and Neuropathy Impairment Score (NIS). The primary objective was to determine the maximum tolerated dose (MTD) of PRX004.ResultsOverall, 21 patients with ATTRv amyloidosis completed the dose-escalation phase; 17 subsequently enrolled in the LTE. The MTD was not reached. PRX004 was well tolerated at all doses, with dose-proportional exposure. GLS and NIS were improved or maintained over 9 months (n = 7).ConclusionsPRX004 was well tolerated in patients with ATTRv amyloidosis and demonstrated potential clinical activity. A phase 2 randomised controlled trial in ATTR cardiomyopathy is ongoing (NCT05442047).

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