First-in-Human Phase I/II Study of NEOD001 in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction
Morie A Gertz1, Heather Landau2, Raymond L Comenzo2
1Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; David Seldin, Boston University, Boston, MA; Brendan Weiss, University of Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy; Stefan Schönland, University of Heidelberg, Heidelberg, Germany; Jackie Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA gertz.morie@mayo.edu.
NEOD001, a novel antibody therapy, shows promising safety and efficacy in treating light chain (AL) amyloidosis. Monthly infusions of NEOD001 at 24 mg/kg are well-tolerated and demonstrate significant organ response rates in patients with persistent organ dysfunction.
Area of Science:
- Hematology
- Immunology
- Clinical Pharmacology
Background:
- Light chain (AL) amyloidosis results from misfolded protein accumulation, leading to vital organ dysfunction.
- NEOD001 is a monoclonal antibody designed to target and clear these misfolded proteins.
Purpose of the Study:
- To assess the safety, tolerability, and optimal dosage of NEOD001 in patients with AL amyloidosis and persistent organ dysfunction.
- To evaluate the pharmacokinetic profile and immunogenicity of NEOD001.
- To determine the efficacy of NEOD001 in improving organ function.
Main Methods:
- A Phase I/II dose-escalation study (NCT01707264) involving 27 patients with AL amyloidosis.
- Intravenous NEOD001 administered every 28 days, with dose levels ranging from 0.5 to 24 mg/kg.
- Safety assessments included maximum tolerated dose, adverse events, and dose-limiting toxicities; efficacy was evaluated using consensus criteria for cardiac and renal response.
Main Results:
- NEOD001 was safe and well-tolerated, with no drug-related serious adverse events or dose-limiting toxicities reported.
- The recommended dose for future studies was determined to be 24 mg/kg, with pharmacokinetics supporting monthly administration.
- Significant organ response rates were observed: 57% cardiac response and 60% renal response among evaluable patients.
Conclusions:
- Monthly NEOD001 infusions are safe and well-tolerated in patients with AL amyloidosis.
- NEOD001 demonstrates favorable organ response rates compared to chemotherapy, establishing it as a potential new therapeutic option.
- Phase II expansion and Phase III studies are underway to further investigate NEOD001's therapeutic potential.
