Company: PRTA
Filing Date: 2025-05-08
Form Type: 10-Q
Source: 0001559053-25-000023
Chunk: 27

Company: PROTHENA CORP PUBLIC LTD CO
Filing Date: 2025-05-08
Form: 10-Q
Item: Part I, Item 2
Chunk 27
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 deposition.

Clinical Development Program for Birtamimab

Birtamimab reacts with a “cryptic” epitope that is exposed on misfolded kappa and lambda light chains that misfold and form amyloid. The epitope is well defined and highly conserved in light chains and exposed from early stages of aggregation throughout amyloid. Preclinical research has demonstrated that birtamimab binds to both soluble and insoluble aggregated kappa and lambda immunoglobulin light chain by recognizing this epitope that is exposed at the earliest stages of abnormal light chain misfolding and through aggregation of deposited amyloid. Our extensive preclinical findings and publications describe two proposed mechanisms of action for birtamimab: binding and neutralization of soluble toxic light chain aggregates, and clearance of amyloid deposits by phagocytosis.

In multiple clinical trials, birtamimab has been shown to be generally safe and well tolerated and has been evaluated in 302 patients receiving monthly intravenous infusions (including 294 patients who received the recommended 24 mg/kg dose), for an average of approximately 15 months.

Confirmatory Phase 3 AFFIRM-AL Clinical Trial Design under SPA Agreement with FDA

Based on further analyses of data from the VITAL clinical trial and multiple in-depth discussions with the FDA, Prothena announced plans in February 2021, to advance birtamimab into the confirmatory Phase 3 AFFIRM-AL clinical trial in patients with Mayo Stage IV AL amyloidosis. AFFIRM-AL is a registration-enabling Phase 3 clinical trial that is being conducted with a primary endpoint of time to all-cause mortality at p<0.10 under a Special Protocol Assessment (SPA) agreement with the FDA. AFFIRM-AL topline trial results are expected in the second quarter of 2025.

AFFIRM-AL is an ongoing global, multi-center, double-blind, placebo-controlled, 2:1 randomized, time-to-event trial e xpected to enroll up to 220 newly diagnosed, treatment naïve patients with AL amyloidosis categorized as Mayo Stage IV. Patients receive 24 mg/kg of birtamimab or placebo by intravenous infusion every 28 days, with all patients receiving concurrent standard of care chemotherapy in accordance with the institutional standard of care which includes a bortezomib-containing chemotherapy r egimen such as c yclophosphamide, bortezomib, and dexamethasone (CyBorD). The initiation of