AL Amyloidosis

AL amyloidosis is a rare, progressive and fatal disease where clonal plasma cells overproduce 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 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. Current treatment strategies target plasma cells to reduce production of new amyloid, but do not address the amyloid already deposited in organs. Mortality is driven primarily by cardiac failure. There is an urgent unmet medical need for therapies that improve survival in patients at risk for early mortality due to amyloid deposition.

Birtamimab, formerly known as NEOD001, is an investigational 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.

In preclinical studies, birtamimab has been shown to broadly react with a “cryptic” epitope that is exposed on misfolded kappa and lambda light chains that misfold and form amyloid. The proposed mechanism of action of birtamimab is to clear amyloid from organs and neutralize soluble aggregates that circulate in the bloodstream.

Birtamimab has been tested in nearly 300 patients with AL amyloidosis at the intended clinical dose of 24 mg/kg and was shown to be generally safe and well tolerated in the clinical studies conducted to date. Birtamimab was previously evaluated in the Phase 3 VITAL Study, a global multi-center, randomized, double-blind, placebo-controlled clinical study of newly diagnosed, treatment naïve patients with AL amyloidosis and cardiac involvement. Results from the analysis of patients categorized as Mayo Stage IV at baseline in the VITAL study 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 placebo-controlled study. Prothena is advancing birtamimab into the confirmatory Phase 3 AFFIRM-AL study in patients with AL amyloidosis categorized as Mayo Stage IV.

Birtamimab has been granted orphan drug designation for AL Amyloidosis by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency and has been granted Fast Track designation by the FDA.