The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease
Crizanlizumab is a monoclonal antibody that binds to P-selectin. On October 28, 2020, a conditional marketing authorization valid through the European Union (EU) was issued for crizanlizumab for the prevention of recurrent vaso-occlusive crises (VOCs) in patients with sickle cell disease aged 16 yea...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-07-01
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| Series: | HemaSphere |
| Online Access: | http://journals.lww.com/10.1097/HS9.0000000000000604 |
| _version_ | 1797281903635595264 |
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| author | Julio Delgado Caroline Voltz Milena Stain Tuomo Lapveteläinen Susanne Urach Johanna Lähteenvuo Karri Penttilä Christian Gisselbrecht Harald Enzmann Francesco Pignatti |
| author_facet | Julio Delgado Caroline Voltz Milena Stain Tuomo Lapveteläinen Susanne Urach Johanna Lähteenvuo Karri Penttilä Christian Gisselbrecht Harald Enzmann Francesco Pignatti |
| author_sort | Julio Delgado |
| collection | DOAJ |
| description | Crizanlizumab is a monoclonal antibody that binds to P-selectin. On October 28, 2020, a conditional marketing authorization valid through the European Union (EU) was issued for crizanlizumab for the prevention of recurrent vaso-occlusive crises (VOCs) in patients with sickle cell disease aged 16 years or older. Crizanlizumab was evaluated in a phase 2, double-blind, placebo-controlled randomized multicenter trial comparing high-dose (5 mg/kg) crizanlizumab, low-dose (2.5 mg/kg) crizanlizumab and placebo in patients with a history of 2–10 VOCs in the previous year. Patients who were receiving concomitant hydroxycarbamide (HC) as well as those not receiving HC were included in the study. The primary endpoint of the trial was the annual rate of sickle cell-related pain crises as adjudicated by a central review committee. High-dose crizanlizumab led to a 45.3% lower median annual rate of sickle cell-related pain crises compared to placebo (P = 0.010), with no statistically significant difference for the low dose. Treatment with high-dose crizanlizumab led to similar incidences of adverse events (AEs), grade 3 AEs, and serious AEs compared to placebo. Most frequently observed AEs that occurred more often in the crizanlizumab arm compared to placebo were infusion related reactions (34.8% versus 21%), arthralgia (18.2% versus 8.1%), diarrhea (10.6% versus 3.2%), and nausea (18.2% versus 11.3%). The aim of this article is to summarize the scientific review of the application leading to regulatory approval in the EU. |
| first_indexed | 2024-03-07T17:04:10Z |
| format | Article |
| id | doaj.art-c1b190f2755848fa85807fd6f89529fa |
| institution | Directory Open Access Journal |
| issn | 2572-9241 |
| language | English |
| last_indexed | 2024-03-07T17:04:10Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj.art-c1b190f2755848fa85807fd6f89529fa2024-03-03T02:51:22ZengWileyHemaSphere2572-92412021-07-0157e60410.1097/HS9.0000000000000604202107000-00017The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell DiseaseJulio Delgado0Caroline Voltz1Milena Stain2Tuomo Lapveteläinen3Susanne Urach4Johanna Lähteenvuo5Karri Penttilä6Christian Gisselbrecht7Harald Enzmann8Francesco Pignatti91 Oncology & Haematology Office, European Medicines Agency, Amsterdam, The Netherlands1 Oncology & Haematology Office, European Medicines Agency, Amsterdam, The Netherlands3 Bundesamt fur Sicherheit im Gesundheitswesen, Vienna, Austria4 Committe for Medicinal Products for Human Use, European Medicines Agency, Amsterdam, The Netherlands3 Bundesamt fur Sicherheit im Gesundheitswesen, Vienna, Austria4 Committe for Medicinal Products for Human Use, European Medicines Agency, Amsterdam, The Netherlands5 Lääkealan turvallisuus- ja kehittämiskeskus, Fimea, Finland6 Hopital Saint Louis, Paris, France4 Committe for Medicinal Products for Human Use, European Medicines Agency, Amsterdam, The Netherlands1 Oncology & Haematology Office, European Medicines Agency, Amsterdam, The NetherlandsCrizanlizumab is a monoclonal antibody that binds to P-selectin. On October 28, 2020, a conditional marketing authorization valid through the European Union (EU) was issued for crizanlizumab for the prevention of recurrent vaso-occlusive crises (VOCs) in patients with sickle cell disease aged 16 years or older. Crizanlizumab was evaluated in a phase 2, double-blind, placebo-controlled randomized multicenter trial comparing high-dose (5 mg/kg) crizanlizumab, low-dose (2.5 mg/kg) crizanlizumab and placebo in patients with a history of 2–10 VOCs in the previous year. Patients who were receiving concomitant hydroxycarbamide (HC) as well as those not receiving HC were included in the study. The primary endpoint of the trial was the annual rate of sickle cell-related pain crises as adjudicated by a central review committee. High-dose crizanlizumab led to a 45.3% lower median annual rate of sickle cell-related pain crises compared to placebo (P = 0.010), with no statistically significant difference for the low dose. Treatment with high-dose crizanlizumab led to similar incidences of adverse events (AEs), grade 3 AEs, and serious AEs compared to placebo. Most frequently observed AEs that occurred more often in the crizanlizumab arm compared to placebo were infusion related reactions (34.8% versus 21%), arthralgia (18.2% versus 8.1%), diarrhea (10.6% versus 3.2%), and nausea (18.2% versus 11.3%). The aim of this article is to summarize the scientific review of the application leading to regulatory approval in the EU.http://journals.lww.com/10.1097/HS9.0000000000000604 |
| spellingShingle | Julio Delgado Caroline Voltz Milena Stain Tuomo Lapveteläinen Susanne Urach Johanna Lähteenvuo Karri Penttilä Christian Gisselbrecht Harald Enzmann Francesco Pignatti The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease HemaSphere |
| title | The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease |
| title_full | The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease |
| title_fullStr | The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease |
| title_full_unstemmed | The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease |
| title_short | The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease |
| title_sort | european medicines agency review of crizanlizumab for the prevention of recurrent vaso occlusive crises in patients with sickle cell disease |
| url | http://journals.lww.com/10.1097/HS9.0000000000000604 |
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