What Is AL Amyloidosis?

AL amyloidosis is a rare, progressive, and fatal disease where clonal plasma cells produce light chain proteins that misfold, aggregate, and deposit as amyloid in vital organs, such as the heart.1 Prothena has over a decade of commitment to developing treatments for amyloidosis.

What Is AL Amyloidosis With Significant Cardiac Involvement?

The extent of cardiac dysfunction is an important predictor of short- and long-term survival of patients with AL amyloidosis.2 Patients with significant cardiac involvement who are at high risk for early death at diagnosis can be identified with cardiac staging systems, which are based around soluble cardiac biomarker measurements.2,3 Patients with Mayo Stage IV AL amyloidosis are at high risk for early death, with a median overall survival of 6-11 months.3-5

What Is Birtamimab?

Birtamimab, formerly known as NEOD001, is an investigational humanized monoclonal antibody designed to specifically and selectively target and clear the amyloid that accumulates and causes organ dysfunction and failure in patients with AL amyloidosis.6 Birtamimab’s design characteristics were chosen to optimize its mechanism of action via an IgG1 backbone and to reduce the risk of immunogenicity via a humanized amino acid sequence. The long half-life of birtamimab provides the convenience of infrequent administration (every 4 weeks).6

Birtamimab has been granted orphan drug designation for AL amyloidosis by both the FDA and the European Medicines Agency and has been granted Fast Track designation by the FDA.

A post hoc analysis from VITAL, a Phase 3 clinical trial in patients with newly diagnosed AL amyloidosis, suggests that birtamimab may have a significant survival benefit in patients with Mayo Stage IV disease.7 Prothena is advancing birtamimab with the confirmatory Phase 3 AFFIRM-AL clinical trial in patients with confirmed Mayo Stage IV AL amyloidosis (currently enrolling; NCT04973137)

Publications
AL Amyloidosis Studies
2011
2011

Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies8
2012
2012

AL Amyloid Imaging and Therapy with a Monoclonal Antibody to a Cryptic Epitope on Amyloid Fibrils9
2013
2013-2016

Phase 1/2

69 previously diagnosed and treated pts with persistent organ dysfunction

2015
2015-2018

VITAL

260 newly diagnosed, treatment-naïve Mayo Stage I-IV pts

2016
2016-2018

PRONTO

129 previously diagnosed pts with at least partial HR after prior treatment and persistent cardiac dysfunction

2016

First-in-Human Phase I/II Study of NEOD001 in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction6

2A4 Binds Soluble and Insoluble Light Chain Aggregates From AL Amyloidosis Patients and Promotes Clearance of Amyloid Deposits by Phagocytosis10
2018
2018-2021

Light Chain (AL) Amyloidosis: The Journey to Diagnosis1

Epidemiology of AL Amyloidosis: A Real-world Study Using US Claims Data11

Healthcare Resource Utilization and Costs in Amyloid Light-Chain Amyloidosis: A Real-World Study Using US Claims Data12

Untangling the Clinical and Economic Burden of Hospitalization for Cardiac Amyloidosis in the United States13

Work Outcomes Among Patients With Light Chain (AL) Amyloidosis: Findings From Three Patient Cohorts14
2021
2021

AFFIRM-AL

Newly diagnosed treatment-naïve Mayo Stage IV pts

2022
2022

Diagnostic Amyloid Light Chain Amyloidosis Hospitalizations Associated With High Acuity and Cost: Analysis of the Premier Healthcare Database15
2023
2023

In-Hospital Mortality in Amyloid Light Chain Amyloidosis: Analysis of the Premier Healthcare Database16

Health-related Quality of Life Instruments For Clinical Trials in AL Amyloidosis: Report From the Amyloidosis Forum HRQOL Working Group17

Birtamimab Plus Standard of Care in Light Chain Amyloidosis: The Phase 3 Randomized Placebo-Controlled VITAL Trial7

Using a Modified Delphi Panel to Estimate Health Service Utilization for Patients with Advanced and Non-Advanced Systemic Light Chain Amyloidosis18

Association Between Hematologic Response and Change in Health-Related Quality of Life Among Patients With Light Chain (AL) Amyloidosis19
2024
2024

The Mechanism of Action, Pharmacological Characteristics, and Clinical Utility of the Amyloid Depleter Birtamimab for the Potential Treatment of AL Amyloidosis20
AA, amyloid A; AL, light chain; FDA, U.S. Food and Drug Administration; HR, hematologic response; HRQoL, health-related quality of life; pts, patients.
  1. McCausland KL, et al. Patient. 2018;11:207–216.
  2. Muchtar E, et al. Mayo Clin Proc. 2021;96:1546–1577.
  3. Kumar S, et al. J Clin Oncol. 2012;30:989–995.
  4. Abdallah N, et al. Blood Adv. 2021;5:1029–1036.
  5. Barrett CD, et al. JACC Heart Fail. 2019;7:958–966.
  6. Gertz MA, et al. J Clin Oncol. 2016;34:1097–1103.
  7. Gertz MA, et al. Blood. 2023;142:1208–1218.
  8. Wall JS, et al. Front Immunol. 2011;2:32.
  9. Wall JS, et al. PLoS One. 2012;7:e52686.
  10. Renz M, et al. Amyloid. 2016;23:168–177.
  11. Quock TP, et al. Blood Adv. 2018;2:1046–1053.
  12. Quock TP, et al. J Comp Eff Res. 2018;7:549–559.
  13. Quock TP, et al. Clinicoecon Outcome Res. 2019;11:431–439.
  14. Rizio AA, et al. Patient Relat Outcome Meas. 2021;12:339–347.
  15. D'Souza A, et al. J Comp Eff Res. 2022;11:1225–1230.
  16. Quock TP, et al. J Comp Eff Res. 2023;12:e220185.
  17. Rizio AA, et al. Patient Relat Outcome Meas. 2023;14:153–169.
  18. Gertz MA, et al. Clinicoecon Outcomes Res. 2023;15:673–680. 
  19. Rizio AA, et al. Patient Relat Outcome Meas. 2023;14:297–304.
  20. Palladini G, et al. Leuk Lymphoma. 2024;1–11. doi: 10.1080/10428194.2024.2337803. Online ahead of print.