AL Amyloidosis

AL amyloidosis is a rare, progressive and typically fatal disease where clonal plasma cells produce light chain proteins that misfold, aggregate and deposit as amyloid in vital organs such as the heart.

It is estimated that there are 60,000 – 120,000 patients worldwide living with Mayo Stage IV AL amyloidosis. Patients with Mayo Stage IV AL amyloidosis are at high risk for early death, with a median overall survival of less than 6 months.

Advancing AL Amyloidosis Treatment

Discover how Prothena’s mission to make a real impact for patients is driving the development of a potential new treatment for AL amyloidosis.

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Patients with AL amyloidosis can present with a wide range of general symptoms that are common to other conditions such as fatigue, shortness of breath, or edema. The extent of cardiac dysfunction is an important predictor of short- and long-term survival of patients with AL amyloidosis. Patients with 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. Mayo Stage IV patients represent the most severe patients.

Current treatment strategies target plasma cells to reduce production of new light chain proteins, but do not address the toxic light chains and amyloid already deposited in vital organs. Mortality is driven primarily by cardiac failure. Based on clinical data to date, Mayo Stage IV patients represent approximately 30% of AL amyloidosis patients.

Birtamimab, formerly known as NEOD001, is an investigational monoclonal antibody designed to specifically and selectively target and clear toxic light chains and the amyloid that accumulates and causes organ dysfunction and failure in patients with AL amyloidosis.

In preclinical studies, birtamimab has been shown to broadly react with a “cryptic” epitope that is exposed only on misfolded toxic kappa and lambda light chains. Birtamimab has a potential best-in-class anti-amyloid mechanism designed to neutralize toxic soluble aggregates and remove insoluble amyloid deposits in patients with AL amyloidosis with cardiac involvement.

Birtamimab has been tested in over 300 patients with AL amyloidosis at the intended clinical dose of 24 mg/kg and was shown to be generally well tolerated in the clinical trials conducted to date. Birtamimab was previously evaluated in the Phase 3 VITAL clinical trial, a global multi-center, randomized, double-blind, placebo-controlled clinical trial of newly diagnosed, treatment naïve patients with AL amyloidosis with cardiac involvement. Results from the post hoc analysis of patients categorized as Mayo Stage IV at baseline (n=77) in the VITAL clinical trial revealed a significant survival benefit favoring birtamimab in these patients, with 74% of birtamimab-treated patients alive at 9 months versus 49% of patients in the control group.

Birtamimab is the only investigational therapeutic that has shown a significant survival benefit in Mayo Stage IV patients with AL amyloidosis in a post hoc analysis of a placebo-controlled study. Based on multiple in-depth discussions with the U.S. Food and Drug Administration (FDA) regarding these results, Prothena has advanced birtamimab into the confirmatory Phase 3 AFFIRM-AL clinical trial in patients with Mayo Stage IV AL amyloidosis. This registration-enabling study will be conducted with a primary endpoint of all-cause mortality at a significance level of 0.10 under a Special Protocol Assessment (SPA) agreement with the FDA.

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. Birtamimab is an investigational drug and not approved by any regulatory authority. To learn more about the AFFIRM-AL clinical trial contact us at AFFIRMALClinicalTrials@prothena.com or visit http://www.AFFIRM-AL.com.