Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification
Introduction: Patients with end-stage kidney disease (ESKD) exhibit anemia, chronic kidney disease‒mineral bone disorder (CKD–MBD), and cardiovascular disease. The REN-001 and REN-002 phase II, multicenter, randomized studies examined safety, tolerability, and effects of sotatercept, an ActRIIA-IgG1...
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doaj-0bccf5654da24b36b96c0047fa7d3a782020-11-25T01:26:22ZengElsevierKidney International Reports2468-02492019-11-0141115851597Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular CalcificationDaniel W. Coyne0Hem N. Singh1William T. Smith2Ana Carolina Giuseppi3Jamie N. Connarn4Matthew L. Sherman5Frank Dellanna6Hartmut H. Malluche7Keith A. Hruska8Department of Medicine, Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri, USACelgene Corporation, Summit, New Jersey, USACelgene Corporation, Summit, New Jersey, USACelgene Corporation, Summit, New Jersey, USACelgene Corporation, Summit, New Jersey, USAAcceleron Pharma Inc., Cambridge, Massachusetts, USAMVZ Davita Rhein-Ruhr, Düsseldorf, GermanyDivision of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, Kentucky, USADepartment of Medicine, Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri, USA; Correspondence: Keith A. Hruska, Departments of Pediatrics, Medicine, and Cell Biology, Rm 5109, MPRB Building, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.Introduction: Patients with end-stage kidney disease (ESKD) exhibit anemia, chronic kidney disease‒mineral bone disorder (CKD–MBD), and cardiovascular disease. The REN-001 and REN-002 phase II, multicenter, randomized studies examined safety, tolerability, and effects of sotatercept, an ActRIIA-IgG1 fusion protein trap, on hemoglobin concentration; REN-001 also explored effects on bone mineral density (BMD) and abdominal aortic vascular calcification. Methods: Forty-three patients were treated in REN-001 (dose range: sotatercept 0.3‒0.7 mg/kg or placebo subcutaneously [s.c.] for 200 days) and 50 in REN-002 (dose range: 0.1‒0.4 mg/kg i.v. and 0.13‒0.5 mg/kg s.c. for 99 days). Results: In REN-001, frequency of achieving target hemoglobin response (>10 g/dl [6.21 mmol/l]) with sotatercept was dose-related and greater than placebo (0.3 mg/kg: 33.3%; 0.5 mg/kg: 62.5%; 0.7 mg/kg: 77.8%; 0.7 mg/kg [doses 1 and 2]/0.4 mg/kg [doses 3‒15]: 33.3%; placebo: 27.3%). REN-002 hemoglobin findings were similar (i.v.: 16.7%−57.1%; s.c.: 11.1%‒42.9%). Dose-related achievement of ≥2% increase in femoral neck cortical BMD was seen among only REN-001 patients receiving sotatercept (0.3‒0.7 mg/kg: 20.0%‒57.1%; placebo: 0.0%). Abdominal aortic vascular calcification was slowed in a dose-related manner, with a ≤15% increase in Agatston score achieved by more REN-001 sotatercept versus placebo patients (60%‒100% vs. 16.7%). The most common adverse events during treatment were hypertension, muscle spasm, headache, arteriovenous fistula site complication, and influenza observed in both treatment and placebo groups. Conclusion: In patients with ESKD, sotatercept exhibited a favorable safety profile and was associated with trends in dose-related slowing of vascular calcification. Less-consistent trends in improved hemoglobin concentration and BMD were observed. Keywords: bone mineral density, end-stage kidney disease, hemoglobin, pharmacodynamics, sotatercept, vascular calcificationhttp://www.sciencedirect.com/science/article/pii/S2468024919314445 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daniel W. Coyne Hem N. Singh William T. Smith Ana Carolina Giuseppi Jamie N. Connarn Matthew L. Sherman Frank Dellanna Hartmut H. Malluche Keith A. Hruska |
spellingShingle |
Daniel W. Coyne Hem N. Singh William T. Smith Ana Carolina Giuseppi Jamie N. Connarn Matthew L. Sherman Frank Dellanna Hartmut H. Malluche Keith A. Hruska Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification Kidney International Reports |
author_facet |
Daniel W. Coyne Hem N. Singh William T. Smith Ana Carolina Giuseppi Jamie N. Connarn Matthew L. Sherman Frank Dellanna Hartmut H. Malluche Keith A. Hruska |
author_sort |
Daniel W. Coyne |
title |
Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification |
title_short |
Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification |
title_full |
Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification |
title_fullStr |
Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification |
title_full_unstemmed |
Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification |
title_sort |
sotatercept safety and effects on hemoglobin, bone, and vascular calcification |
publisher |
Elsevier |
series |
Kidney International Reports |
issn |
2468-0249 |
publishDate |
2019-11-01 |
description |
Introduction: Patients with end-stage kidney disease (ESKD) exhibit anemia, chronic kidney disease‒mineral bone disorder (CKD–MBD), and cardiovascular disease. The REN-001 and REN-002 phase II, multicenter, randomized studies examined safety, tolerability, and effects of sotatercept, an ActRIIA-IgG1 fusion protein trap, on hemoglobin concentration; REN-001 also explored effects on bone mineral density (BMD) and abdominal aortic vascular calcification. Methods: Forty-three patients were treated in REN-001 (dose range: sotatercept 0.3‒0.7 mg/kg or placebo subcutaneously [s.c.] for 200 days) and 50 in REN-002 (dose range: 0.1‒0.4 mg/kg i.v. and 0.13‒0.5 mg/kg s.c. for 99 days). Results: In REN-001, frequency of achieving target hemoglobin response (>10 g/dl [6.21 mmol/l]) with sotatercept was dose-related and greater than placebo (0.3 mg/kg: 33.3%; 0.5 mg/kg: 62.5%; 0.7 mg/kg: 77.8%; 0.7 mg/kg [doses 1 and 2]/0.4 mg/kg [doses 3‒15]: 33.3%; placebo: 27.3%). REN-002 hemoglobin findings were similar (i.v.: 16.7%−57.1%; s.c.: 11.1%‒42.9%). Dose-related achievement of ≥2% increase in femoral neck cortical BMD was seen among only REN-001 patients receiving sotatercept (0.3‒0.7 mg/kg: 20.0%‒57.1%; placebo: 0.0%). Abdominal aortic vascular calcification was slowed in a dose-related manner, with a ≤15% increase in Agatston score achieved by more REN-001 sotatercept versus placebo patients (60%‒100% vs. 16.7%). The most common adverse events during treatment were hypertension, muscle spasm, headache, arteriovenous fistula site complication, and influenza observed in both treatment and placebo groups. Conclusion: In patients with ESKD, sotatercept exhibited a favorable safety profile and was associated with trends in dose-related slowing of vascular calcification. Less-consistent trends in improved hemoglobin concentration and BMD were observed. Keywords: bone mineral density, end-stage kidney disease, hemoglobin, pharmacodynamics, sotatercept, vascular calcification |
url |
http://www.sciencedirect.com/science/article/pii/S2468024919314445 |
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