Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis by Duncan B. Richards, Louise M. Cookson,

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Presentation transcript:

Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis by Duncan B. Richards, Louise M. Cookson, Sharon V. Barton, Lia Liefaard, Thirusha Lane, David F. Hutt, James M. Ritter, Marianna Fontana, James C. Moon, Julian D. Gillmore, Ashutosh Wechalekar, Philip N. Hawkins, and Mark B. Pepys Sci Transl Med Volume 10(422):eaan3128 January 3, 2018 Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

Fig. 1 Pharmacokinetics of dezamizumab in patients with systemic amyloidosis. Pharmacokinetics of dezamizumab in patients with systemic amyloidosis. The pharmacokinetics of dezamizumab are shown here in two subjects, illustrating how plasma clearance of the antibody changes with progressive reduction of hepatic amyloid load. Subject 013 received 650 mg of dezamizumab in part A () and 600 mg in part B (). Subject 016 received an ineffective first antibody dose in part A but then received an effective second dose of 2000 mg in part B () followed by a further 2000-mg third dose in part B (). Duncan B. Richards et al., Sci Transl Med 2018;10:eaan3128 Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

Fig. 2 Effect on amyloid load of miridesap followed by dezamizumab. Effect on amyloid load of miridesap followed by dezamizumab. (A) Anterior views of radiolabelled serum amyloid P component (SAP) scintigraphy scans for amyloid in subject 014 with systemic immunoglobulin light chain (AL) amyloidosis. Images shown are for before treatment (left), 42 days after first dezamizumab dose (center), and 42 days after second dezamizumab dose (right). (B) Posterior views of radiolabelled SAP scintigraphy scans for amyloid in subject 017 with hereditary systemic fibrinogen A α-chain (AFib) amyloidosis. Images shown are before treatment (left) and 42 days after dezamizumab treatment (right). Duncan B. Richards et al., Sci Transl Med 2018;10:eaan3128 Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

Fig. 3 Liver stiffness and NT-proBNP concentration after treatment with miridesap followed by dezamizumab. Liver stiffness and NT-proBNP concentration after treatment with miridesap followed by dezamizumab. (A and B) Serial measurements of liver stiffness using transient elastography after the start of dezamizumab infusion on day 1 in subjects with hepatic amyloidosis. Predose measurements before each dezamizumab infusion are indicated by PD. Median normal liver stiffness, 5.3 kPa (90% of individuals are <7.0 kPa). (A) Graph shows subjects with initial baseline liver stiffness ≤15kPa. Subject 007 () received sequential doses of 152, 600, and 2000 mg of dezamizumab. Subject 008 () received sequential doses of 246 and 600 mg. Subject 013 () received sequential doses of 650 and 600 mg. Subject 014 () received sequential doses of 600, 1000, and 500 mg. Subject 015 () received sequential doses of 600 and 2000 mg. (B) Graph shows subjects with initial baseline liver stiffness >15kPa. Subject 009 () received sequential doses of 637, 1000, and 2000 mg. Subject 010 () received sequential doses of 400, 1200, and 2000 mg. Subject 011 () received sequential doses of 650, 1000, and 2000 mg. Subject 016 () received sequential doses of 600, 2000, and 2000 mg. Subject 019 () received a single dose of 2000 mg. The interval between doses was variable: range, 3 to 12 months. (C) Serial measurements of the concentration of circulating NT-proBNP after dezamizumab treatment in subjects with proven cardiac amyloidosis. All available results are shown. S, value at screening before study; PD, predose value before each dezamizumab infusion; NT-proBNP, N-terminal pro–B-type natriuretic peptide. Results after first dose are shown on an expanded scale. Subject 018 (AL type) () received sequential doses of 600, 1200, and 1200 mg of dezamizumab. Subject 020 (AL) () received a single dose of 600 mg. Subject 021 (AL) () received sequential doses of 600, 1200, and 1200 mg. Subject 023 [transthyretin amyloidosis (ATTR)] () received a single dose of 1200 mg. Subject 024 (ATTR) () received a single dose of 1000 mg. Subject 025 (ATTR) () received a single dose of 600 mg. The interval between doses was variable: range, 2 to 3 months. Duncan B. Richards et al., Sci Transl Med 2018;10:eaan3128 Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works