Organ response in patients with AL amyloidosis treated with NEOD001, an amyloid‐directed monoclonal antibody

Bifunctional amyloid-reactive peptide promotes binding of antibody 11-1F4 to diverse amyloid types and enhances therapeutic efficacy

“…For these patients, removal of amyloid deposits may stabilize or improve organ function. To this end, a new therapeutic paradigm has been developed for the treatment of patients with systemic amyloidosis; namely, the use of amyloid-directed passive immunotherapy using the humanized mAbs NEDO001 (12,23,30), dezamizumab (31), and the chimeric reagent 11-1F4 (11). All three mAb have demonstrated an excellent safety profile at the doses used (∼15-24 mg/kg).…”

“…All three mAb have demonstrated an excellent safety profile at the doses used (∼15-24 mg/kg). Clinical evaluation of these mAbs has shown them capable of reducing amyloid load (13,31) and improving surrogate biomarkers of cardiac and renal function (11,30). Despite promising early-phase data from all these clinical trials, a recent placebo-controlled phase 2 clinical trial of mAb NEOD001 failed to meet primary outcomes, and the development of this drug was halted.…”

Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis

“…Despite unequivocal evidence of reduction in renal amyloid load, effects on proteinuria and preservation of renal function will require a longer followup than the 6 weeks of the present protocol. Other than preliminary examination of safety in the six cardiac amyloidosis patients reported in this study, the use of miridesap and dezamizumab in subjects with heart involvement will be explored in our forthcoming phase does not elicit any systemic reaction and, in contrast to the rapid amyloid loadrelated clearance of dezamizumab, the 13 to 16day plasma halflife of NEOD001 approaches that of free immunoglobulin G (15). Infusion of 111F4 produces systemic reactions and rashes and the antibody demonstrably bound to amyloid in 9 of 18 reported AL cases (17).…”

A validated composite organ and hematologic response model for early assessment of treatment outcomes in light chain amyloidosis

“…It may also identify patients who have not achieved a deep HR, but can safely continue first line therapy if they have achieved an OR. Such a surrogate model may also be helpful in light of new, emerging therapies that target the amyloid fibril and can potentially lead to earlier OR 18,19 .…”