Table 3. Antiamyloid therapies currently... | American Society of Hematology

Table 3.

Antiamyloid therapies currently under development for AL amyloidosis

Agent	Target	Comments
CAEL-101	Amyloid fibrils	• Targets amyloid deposits in vivo as assessed by imaging studies • Promising results in preliminary uncontrolled studies⁹⁴ • Phase 3 trials comparing CyBorD vs CyBorD plus CAEL-101 in stage IIIa (NCT04512235) and IIIb (NCT04504825) subjects are ongoing
Birtamimab	Amyloid fibrils	• Post hoc analysis of the phase 3 study of birtamimab vs placebo plus bortezomib-based upfront therapy suggests survival benefit in Mayo Clinic 2012 stage IV patients • A trial is now planned in Mayo Clinic 2012 stage IV patients
Doxycycline	Amyloid deposits Amyloid light chains	• Reduces LC proteotoxicity and inhibits the formation of and disrupts amyloid fibrils in animal models^95,96 • Two retrospective controlled studies reported a survival advantage with doxycycline^97,98 • A phase 2 trial of doxycycline in conjunction with bortezomib-based chemotherapy showed low early mortality rates⁹⁹ • An international randomized phase 3 trial of bortezomib-based therapy with or without doxycycline is ongoing (NCT03474458) • A Chinese randomized phase 3 trial of CyBorD with or without doxycycline showed no improvement of progression free survival (NCT03401372)¹⁰⁰

Agent	Target	Comments
CAEL-101	Amyloid fibrils	• Targets amyloid deposits in vivo as assessed by imaging studies • Promising results in preliminary uncontrolled studies⁹⁴ • Phase 3 trials comparing CyBorD vs CyBorD plus CAEL-101 in stage IIIa (NCT04512235) and IIIb (NCT04504825) subjects are ongoing
Birtamimab	Amyloid fibrils	• Post hoc analysis of the phase 3 study of birtamimab vs placebo plus bortezomib-based upfront therapy suggests survival benefit in Mayo Clinic 2012 stage IV patients • A trial is now planned in Mayo Clinic 2012 stage IV patients
Doxycycline	Amyloid deposits Amyloid light chains	• Reduces LC proteotoxicity and inhibits the formation of and disrupts amyloid fibrils in animal models^95,96 • Two retrospective controlled studies reported a survival advantage with doxycycline^97,98 • A phase 2 trial of doxycycline in conjunction with bortezomib-based chemotherapy showed low early mortality rates⁹⁹ • An international randomized phase 3 trial of bortezomib-based therapy with or without doxycycline is ongoing (NCT03474458) • A Chinese randomized phase 3 trial of CyBorD with or without doxycycline showed no improvement of progression free survival (NCT03401372)¹⁰⁰