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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933454/ https://www.ncbi.nlm.nih.gov/pubmed/31891000 http://dx.doi.org/10.1016/j.ekir.2019.08.001 |
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author | Coyne, Daniel W. Singh, Hem N. Smith, William T. Giuseppi, Ana Carolina Connarn, Jamie N. Sherman, Matthew L. Dellanna, Frank Malluche, Hartmut H. Hruska, Keith A. |
author_facet | Coyne, Daniel W. Singh, Hem N. Smith, William T. Giuseppi, Ana Carolina Connarn, Jamie N. Sherman, Matthew L. Dellanna, Frank Malluche, Hartmut H. Hruska, Keith A. |
author_sort | Coyne, Daniel W. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6933454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-69334542019-12-30 Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification Coyne, Daniel W. Singh, Hem N. Smith, William T. Giuseppi, Ana Carolina Connarn, Jamie N. Sherman, Matthew L. Dellanna, Frank Malluche, Hartmut H. Hruska, Keith A. Kidney Int Rep Clinical Research 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. Elsevier 2019-08-13 /pmc/articles/PMC6933454/ /pubmed/31891000 http://dx.doi.org/10.1016/j.ekir.2019.08.001 Text en © 2019 International Society of Nephrology. Published by Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Clinical Research Coyne, Daniel W. Singh, Hem N. Smith, William T. Giuseppi, Ana Carolina Connarn, Jamie N. Sherman, Matthew L. Dellanna, Frank Malluche, Hartmut H. Hruska, Keith A. Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification |
title | 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_short | Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification |
title_sort | sotatercept safety and effects on hemoglobin, bone, and vascular calcification |
topic | Clinical Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933454/ https://www.ncbi.nlm.nih.gov/pubmed/31891000 http://dx.doi.org/10.1016/j.ekir.2019.08.001 |
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