Rare Daily Staff
Prothena said it will conduct a confirmatory phase 3 study of its experimental drug birtamimab in AL amyloidosis after conducting further analyses and holding discussions with the U.S. Food and Drug Administration.
In 2018 Prothena said it would discontinue development of the experimental antibody after an independent data monitoring committee conducted an analysis of a late-stage study and recommended discontinuation for futility. The registration-enabling study will be conducted with a primary endpoint of all-cause mortality under a Special Protocol Assessment agreement with the FDA.
AL amyloidosis is part of a complex group of diseases caused by tissue deposition of misfolded proteins that result in progressive organ damage. AL amyloidosis, the most common type, is rare, progressive, and typically fatal. Soluble toxic aggregates and deposited amyloid lead to progressive failure of vital organs including the heart, kidneys and nervous system, causing significant morbidity and mortality.
Birtamimab is an investigational humanized immunoglobulin G1 designed to directly neutralize soluble toxic aggregates and promote clearance of amyloid via phagocytosis. It targets misfolded protein and clears deposited amyloid that causes organ dysfunction and failure in patients with AL amyloidosis. In clinical studies, birtamimab was generally safe and well tolerated.
Birtamimab has been granted Fast Track Designation by the FDA for the treatment of Mayo Stage IV patients with AL amyloidosis to reduce the risk of mortality and has been granted Orphan Drug designation by both the FDA and European Medicines Agency.
The company said birtamimab is the only experimental therapeutic that has shown a significant survival benefit in Mayo Stage IV patients with AL amyloidosis in a placebo-controlled study, with 74 percent of birtamimab-treated patients alive at 9 months versus 49 percent of patients in the control group in VITAL. AFFIRM-AL is expected to initiate mid-2021.
The significant survival benefit observed in VITAL with birtamimab was further supported by evidence of clinical benefit on secondary endpoints, including significant changes observed on both the Short Form-36 version 2 Physical Component Score (SF-36v2 PCS), a measure of quality of life, and six Minute Walk Test distance, an assessment of functional capacity.
“Our analysis of the previously disclosed VITAL results revealed a greater than 50 percent relative risk reduction for all-cause mortality in Mayo Stage IV patients treated with birtamimab,” said Gene Kinney, president and CEO of Prothena. “We have extensively reviewed these results during a series of formal and informal interactions with the FDA and are appreciative of the close collaboration that led to this unprecedented SPA agreement for the AFFIRM-AL study. Birtamimab becomes our most advanced late-stage program and now has a defined path forward in this orphan patient population.”
Photo: Gene Kinney, president and CEO of Prothena
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