Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial

BORA study investigators

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that has been shown to safely reduce exacerbations and improve lung function for patients with asthma. We assessed the long-term safety and efficacy of benralizumab for patients with severe, uncontrolled eosinophilic asthma. Methods: We conducted a randomised, double-blind, parallel-group, phase 3 extension study at 447 sites in 24 countries. Eligible patients had to have completed the SIROCCO or CALIMA trials and remained on subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W). Patients who had received placebo in those trials were re-randomised in a 1:1 ratio, using an interactive web-based system, to benralizumab 30 mg either Q4W or Q8W (first three doses 4 weeks apart). Treatment lasted for 56 weeks for adult patients (age ≥18 years) and 108 weeks for adolescent patients (age 12–17 years). The primary endpoint was the safety and tolerability of the two dosing regimens of benralizumab up to 68 weeks for adult patients (including the follow-up visit post-treatment) and up to 56 weeks for adolescent patients. This endpoint was assessed in the full analysis set, which included all patients from the SIROCCO and CALIMA predecessor studies who received at least one dose of study treatment in BORA and did not continue into another trial. This study is registered with ClinicalTrials.gov (NCT02258542). Findings: Between Nov 19, 2014, and July 6, 2016, we enrolled 1926 patients, of whom 633 had received benralizumab Q4W and 639 had received benralizumab Q8W in SIROCCO or CALIMA. The remaining 654 patients had received placebo in those trials and were randomly re-assigned in this trial to receive benralizumab Q4W (n=320) or Q8W (n=334). 1576 patients, including 783 who received benralizumab Q4W (265 newly assigned) and 793 who received benralizumab Q8W (281 newly assigned), were included in the full analysis set. The most common adverse events in all groups were viral upper respiratory tract infection (14–16%) and worsening asthma (7–10%). The most common serious adverse events were worsening asthma (3–4%), pneumonia (<1% to 1%), and pneumonia caused by bacterial infection (0–1%). The percentages of patients who had any on-treatment adverse event, any serious adverse event, or any adverse event leading to treatment discontinuation during BORA were similar between patients originally assigned benralizumab and those originally assigned placebo and between benralizumab treatment regimens. The percentage of patients who had any adverse event was similar between SIROCCO or CALIMA (71–75%; benralizumab group only) and BORA (65–71%), as was the percentage of patients who had an adverse event that led to treatment discontinuation (2% in SIROCCO and CALIMA vs 2–3% in BORA). Interpretation: The 2 years of safety results validate that observations observed in the first year of benralizumab continued through a second year of treatment. No new consequences of long-term eosinophil depletion occurred, and the incidence of other adverse events, including opportunistic infections, were similar during the second year. Funding: AstraZeneca and Kyowa Hakko Kirin.

Original languageEnglish
Pages (from-to)46-59
Number of pages14
JournalThe Lancet Respiratory Medicine
Volume7
Issue number1
DOIs
Publication statusPublished - 2019 Jan

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Asthma
Safety
benralizumab
Placebos
Therapeutics
Pneumonia
Interleukin-5 Receptors
Opportunistic Infections
Bacterial Infections
Eosinophils
Respiratory Tract Infections
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

Cite this

@article{63f408dc96ad45259968792cd3bb376f,
title = "Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial",
abstract = "Background: Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that has been shown to safely reduce exacerbations and improve lung function for patients with asthma. We assessed the long-term safety and efficacy of benralizumab for patients with severe, uncontrolled eosinophilic asthma. Methods: We conducted a randomised, double-blind, parallel-group, phase 3 extension study at 447 sites in 24 countries. Eligible patients had to have completed the SIROCCO or CALIMA trials and remained on subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W). Patients who had received placebo in those trials were re-randomised in a 1:1 ratio, using an interactive web-based system, to benralizumab 30 mg either Q4W or Q8W (first three doses 4 weeks apart). Treatment lasted for 56 weeks for adult patients (age ≥18 years) and 108 weeks for adolescent patients (age 12–17 years). The primary endpoint was the safety and tolerability of the two dosing regimens of benralizumab up to 68 weeks for adult patients (including the follow-up visit post-treatment) and up to 56 weeks for adolescent patients. This endpoint was assessed in the full analysis set, which included all patients from the SIROCCO and CALIMA predecessor studies who received at least one dose of study treatment in BORA and did not continue into another trial. This study is registered with ClinicalTrials.gov (NCT02258542). Findings: Between Nov 19, 2014, and July 6, 2016, we enrolled 1926 patients, of whom 633 had received benralizumab Q4W and 639 had received benralizumab Q8W in SIROCCO or CALIMA. The remaining 654 patients had received placebo in those trials and were randomly re-assigned in this trial to receive benralizumab Q4W (n=320) or Q8W (n=334). 1576 patients, including 783 who received benralizumab Q4W (265 newly assigned) and 793 who received benralizumab Q8W (281 newly assigned), were included in the full analysis set. The most common adverse events in all groups were viral upper respiratory tract infection (14–16{\%}) and worsening asthma (7–10{\%}). The most common serious adverse events were worsening asthma (3–4{\%}), pneumonia (<1{\%} to 1{\%}), and pneumonia caused by bacterial infection (0–1{\%}). The percentages of patients who had any on-treatment adverse event, any serious adverse event, or any adverse event leading to treatment discontinuation during BORA were similar between patients originally assigned benralizumab and those originally assigned placebo and between benralizumab treatment regimens. The percentage of patients who had any adverse event was similar between SIROCCO or CALIMA (71–75{\%}; benralizumab group only) and BORA (65–71{\%}), as was the percentage of patients who had an adverse event that led to treatment discontinuation (2{\%} in SIROCCO and CALIMA vs 2–3{\%} in BORA). Interpretation: The 2 years of safety results validate that observations observed in the first year of benralizumab continued through a second year of treatment. No new consequences of long-term eosinophil depletion occurred, and the incidence of other adverse events, including opportunistic infections, were similar during the second year. Funding: AstraZeneca and Kyowa Hakko Kirin.",
author = "{BORA study investigators} and Busse, {William W.} and Bleecker, {Eugene R.} and FitzGerald, {J. Mark} and Ferguson, {Gary T.} and Peter Barker and Stephanie Sproule and Olsson, {Richard F.} and Martin, {Ubaldo J.} and Mitchell Goldman and Anah{\'i} Ya{\~n}ez and Marcelo Fern{\'a}ndez and Alberto Tolcachier and Juan Belloni and Jorge Taborda and {De Salvo}, Maria and Jorge Maspero and Carlos Victorio and Navarta, {Miguel Chirino} and Monica Grilli and Pablo Rodr{\'i}guez and Mar{\'i}a Otaola and V{\'i}ctor Cambursano and Patricia Malamud and Ana Stok and German Arce and Osiris Roza and Fernando Scherbovsky and Pedro Elias and Saez, {Maria Salazan} and Matthew Peters and Martin Phillips and John Upham and Peter Gibson and Francis Thien and Jo Douglass and Paul Thomas and Philip Bardin and Dimitar Sajkov and Mark Hew and David Langton and Andreia Pez and Carlos Fritscher and Jorge Hetzel and Waldo Mattos and Rafael Stelmach and Martti Antila and Fernandes, {Ana Luisa} and Hristo Metev and Yavor Ivanov and Aneliya Bogdanova",
year = "2019",
month = "1",
doi = "10.1016/S2213-2600(18)30406-5",
language = "English",
volume = "7",
pages = "46--59",
journal = "The Lancet Respiratory Medicine",
issn = "2213-2600",
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}

Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma : 1-year results from the BORA phase 3 extension trial. / BORA study investigators.

In: The Lancet Respiratory Medicine, Vol. 7, No. 1, 01.2019, p. 46-59.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma

T2 - 1-year results from the BORA phase 3 extension trial

AU - BORA study investigators

AU - Busse, William W.

AU - Bleecker, Eugene R.

AU - FitzGerald, J. Mark

AU - Ferguson, Gary T.

AU - Barker, Peter

AU - Sproule, Stephanie

AU - Olsson, Richard F.

AU - Martin, Ubaldo J.

AU - Goldman, Mitchell

AU - Yañez, Anahí

AU - Fernández, Marcelo

AU - Tolcachier, Alberto

AU - Belloni, Juan

AU - Taborda, Jorge

AU - De Salvo, Maria

AU - Maspero, Jorge

AU - Victorio, Carlos

AU - Navarta, Miguel Chirino

AU - Grilli, Monica

AU - Rodríguez, Pablo

AU - Otaola, María

AU - Cambursano, Víctor

AU - Malamud, Patricia

AU - Stok, Ana

AU - Arce, German

AU - Roza, Osiris

AU - Scherbovsky, Fernando

AU - Elias, Pedro

AU - Saez, Maria Salazan

AU - Peters, Matthew

AU - Phillips, Martin

AU - Upham, John

AU - Gibson, Peter

AU - Thien, Francis

AU - Douglass, Jo

AU - Thomas, Paul

AU - Bardin, Philip

AU - Sajkov, Dimitar

AU - Hew, Mark

AU - Langton, David

AU - Pez, Andreia

AU - Fritscher, Carlos

AU - Hetzel, Jorge

AU - Mattos, Waldo

AU - Stelmach, Rafael

AU - Antila, Martti

AU - Fernandes, Ana Luisa

AU - Metev, Hristo

AU - Ivanov, Yavor

AU - Bogdanova, Aneliya

PY - 2019/1

Y1 - 2019/1

N2 - Background: Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that has been shown to safely reduce exacerbations and improve lung function for patients with asthma. We assessed the long-term safety and efficacy of benralizumab for patients with severe, uncontrolled eosinophilic asthma. Methods: We conducted a randomised, double-blind, parallel-group, phase 3 extension study at 447 sites in 24 countries. Eligible patients had to have completed the SIROCCO or CALIMA trials and remained on subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W). Patients who had received placebo in those trials were re-randomised in a 1:1 ratio, using an interactive web-based system, to benralizumab 30 mg either Q4W or Q8W (first three doses 4 weeks apart). Treatment lasted for 56 weeks for adult patients (age ≥18 years) and 108 weeks for adolescent patients (age 12–17 years). The primary endpoint was the safety and tolerability of the two dosing regimens of benralizumab up to 68 weeks for adult patients (including the follow-up visit post-treatment) and up to 56 weeks for adolescent patients. This endpoint was assessed in the full analysis set, which included all patients from the SIROCCO and CALIMA predecessor studies who received at least one dose of study treatment in BORA and did not continue into another trial. This study is registered with ClinicalTrials.gov (NCT02258542). Findings: Between Nov 19, 2014, and July 6, 2016, we enrolled 1926 patients, of whom 633 had received benralizumab Q4W and 639 had received benralizumab Q8W in SIROCCO or CALIMA. The remaining 654 patients had received placebo in those trials and were randomly re-assigned in this trial to receive benralizumab Q4W (n=320) or Q8W (n=334). 1576 patients, including 783 who received benralizumab Q4W (265 newly assigned) and 793 who received benralizumab Q8W (281 newly assigned), were included in the full analysis set. The most common adverse events in all groups were viral upper respiratory tract infection (14–16%) and worsening asthma (7–10%). The most common serious adverse events were worsening asthma (3–4%), pneumonia (<1% to 1%), and pneumonia caused by bacterial infection (0–1%). The percentages of patients who had any on-treatment adverse event, any serious adverse event, or any adverse event leading to treatment discontinuation during BORA were similar between patients originally assigned benralizumab and those originally assigned placebo and between benralizumab treatment regimens. The percentage of patients who had any adverse event was similar between SIROCCO or CALIMA (71–75%; benralizumab group only) and BORA (65–71%), as was the percentage of patients who had an adverse event that led to treatment discontinuation (2% in SIROCCO and CALIMA vs 2–3% in BORA). Interpretation: The 2 years of safety results validate that observations observed in the first year of benralizumab continued through a second year of treatment. No new consequences of long-term eosinophil depletion occurred, and the incidence of other adverse events, including opportunistic infections, were similar during the second year. Funding: AstraZeneca and Kyowa Hakko Kirin.

AB - Background: Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that has been shown to safely reduce exacerbations and improve lung function for patients with asthma. We assessed the long-term safety and efficacy of benralizumab for patients with severe, uncontrolled eosinophilic asthma. Methods: We conducted a randomised, double-blind, parallel-group, phase 3 extension study at 447 sites in 24 countries. Eligible patients had to have completed the SIROCCO or CALIMA trials and remained on subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W). Patients who had received placebo in those trials were re-randomised in a 1:1 ratio, using an interactive web-based system, to benralizumab 30 mg either Q4W or Q8W (first three doses 4 weeks apart). Treatment lasted for 56 weeks for adult patients (age ≥18 years) and 108 weeks for adolescent patients (age 12–17 years). The primary endpoint was the safety and tolerability of the two dosing regimens of benralizumab up to 68 weeks for adult patients (including the follow-up visit post-treatment) and up to 56 weeks for adolescent patients. This endpoint was assessed in the full analysis set, which included all patients from the SIROCCO and CALIMA predecessor studies who received at least one dose of study treatment in BORA and did not continue into another trial. This study is registered with ClinicalTrials.gov (NCT02258542). Findings: Between Nov 19, 2014, and July 6, 2016, we enrolled 1926 patients, of whom 633 had received benralizumab Q4W and 639 had received benralizumab Q8W in SIROCCO or CALIMA. The remaining 654 patients had received placebo in those trials and were randomly re-assigned in this trial to receive benralizumab Q4W (n=320) or Q8W (n=334). 1576 patients, including 783 who received benralizumab Q4W (265 newly assigned) and 793 who received benralizumab Q8W (281 newly assigned), were included in the full analysis set. The most common adverse events in all groups were viral upper respiratory tract infection (14–16%) and worsening asthma (7–10%). The most common serious adverse events were worsening asthma (3–4%), pneumonia (<1% to 1%), and pneumonia caused by bacterial infection (0–1%). The percentages of patients who had any on-treatment adverse event, any serious adverse event, or any adverse event leading to treatment discontinuation during BORA were similar between patients originally assigned benralizumab and those originally assigned placebo and between benralizumab treatment regimens. The percentage of patients who had any adverse event was similar between SIROCCO or CALIMA (71–75%; benralizumab group only) and BORA (65–71%), as was the percentage of patients who had an adverse event that led to treatment discontinuation (2% in SIROCCO and CALIMA vs 2–3% in BORA). Interpretation: The 2 years of safety results validate that observations observed in the first year of benralizumab continued through a second year of treatment. No new consequences of long-term eosinophil depletion occurred, and the incidence of other adverse events, including opportunistic infections, were similar during the second year. Funding: AstraZeneca and Kyowa Hakko Kirin.

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U2 - 10.1016/S2213-2600(18)30406-5

DO - 10.1016/S2213-2600(18)30406-5

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JO - The Lancet Respiratory Medicine

JF - The Lancet Respiratory Medicine

SN - 2213-2600

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