Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study

• DOI: 10.1186/s12872-021-02407-6
• Publication Date: 2022-02-13T22:02:25Z
• Authors: Ashutosh Wechalekar; Gunnar Antoni; Wasfi Al Azzam; Mats Bergström; Swethajit Biswas; Chao Chen; Joseph Cheriyan; Matthew Cleveland; Louise Cookson; Paul Galette; Robert L. Janiczek; Raymond Y. Kwong; Mary Ann Lukas; Helen Millns; Duncan Richards; Ian Schneider; Scott D. Solomon; Jens Sörensen; James Storey; Douglas Thompson; Guus van Dongen; Danielle J. Vugts; Anders Wall; Gerhard Wikström; Rodney H. Falk
• Keywords: Pharmacodynamics; Cardiac Amyloidosis

Abstract Background In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of from liver, spleen and kidney in patients systemic amyloidosis. We report results 2 concurrent immuno-positron emission tomography (PET) assessing efficacy, pharmacodynamics, pharmacokinetics, safety cardiac uptake (of dezamizumab) following same intervention Methods Both were uncontrolled open-label studies. After depletion miridesap, received ≤ 6 monthly doses dezamizumab trial (n = 7), non-radiolabelled plus [ 89 Zr]Zr-dezamizumab (total mass dose 80 mg at session 1 500 2) immuno-PET 2). Primary endpoints changed baseline follow-up (at 8 weeks) left ventricular (LVM) magnetic resonance imaging safety. endpoint was assessed via PET. Results Dezamizumab produced no appreciable or consistent reduction LVM nor improvement function study. study, measurable Zr]Zr-dezamizumab, although seen both patients, moderate low. Uptake notably lower patient higher LVM. Treatment-associated rash cutaneous small-vessel vasculitis observed Abdominal large-vessel after initial dosing (300 mg) occurred first immunoglobulin light chain amyloidosis enrolled Symptom resolution nearly complete within 24 h intravenous methylprednisolone discontinuation; abdominal computed weeks. Conclusions Unlike previous observations visceral reduction, there evidence this trial, potentially related limited as demonstrated The benefit-risk assessment for considered unfavourable incidence development indication terminated. Trial registration NCT03044353 (2 February 2017) NCT03417830 (25 January 2018).