Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials
Gili Kenet,1,2 Thomas Moulton,3 Brian M Wicklund,4 Sanjay P Ahuja,5 Miguel Escobar,6 Johnny Mahlangu7 1National Hemophilia Center, Sheba Medical Center, Tel HaShomer, Israel; 2The Amalia Biron Thrombosis Research Institute, Tel Aviv University, Tel Aviv, Israel; 3Bayer, Whippany, NJ, USA; 4Children’...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-06-01
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| Series: | Journal of Blood Medicine |
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| Online Access: | https://www.dovepress.com/switching-from-sucrose-formulated-rfviii-to-octocog-alfa-bay-81-8973-p-peer-reviewed-fulltext-article-JBM |
| _version_ | 1797789384297152512 |
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| author | Kenet G Moulton T Wicklund BM Ahuja SP Escobar M Mahlangu J |
| author_facet | Kenet G Moulton T Wicklund BM Ahuja SP Escobar M Mahlangu J |
| author_sort | Kenet G |
| collection | DOAJ |
| description | Gili Kenet,1,2 Thomas Moulton,3 Brian M Wicklund,4 Sanjay P Ahuja,5 Miguel Escobar,6 Johnny Mahlangu7 1National Hemophilia Center, Sheba Medical Center, Tel HaShomer, Israel; 2The Amalia Biron Thrombosis Research Institute, Tel Aviv University, Tel Aviv, Israel; 3Bayer, Whippany, NJ, USA; 4Children’s Mercy-Kansas City, Kansas City, MO, USA; 5Rainbow Babies & Children’s Hospital, Cleveland, OH, USA; 6University of Texas Health Science Center, Houston, TX, USA; 7Hemophilia Comprehensive Care Center, Faculty of Health Sciences, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand, and National Health Laboratory Service, Johannesburg, South AfricaCorrespondence: Gili Kenet, Amalia Biron Thrombosis Research Institute, Tel Aviv University, Tel HaShomer, 52621, Israel, Tel +972-3-5307356, Fax +972-3-5351806, Email Gili.kenet@sheba.health.gov.ilIntroduction: Previous clinical trials established the efficacy and safety of sucrose-formulated recombinant factor (F) VIII (rFVIII-FS/Kogenate FS®/Helixate FS®) and octocog alfa (BAY 81– 8973/Kovaltry®; LEOPOLD trials).Aim: To report the results of a post hoc subgroup analysis assessing efficacy and safety outcomes in patients with hemophilia A who were receiving rFVIII-FS prior to enrolling into the LEOPOLD I Part B and LEOPOLD Kids Part A clinical trials and switching to octocog alfa.Methods: LEOPOLD I Part B (NCT01029340) and LEOPOLD Kids Part A (NCT01311648) were octocog alfa Phase 3, multinational, open-label studies in patients with severe hemophilia A aged 12– 65 years and ≤ 12 years, respectively. Annualized bleeding rate (ABR) was the efficacy endpoint for both studies. Safety endpoints included adverse events (AEs) and development of FVIII inhibitors.Results: Of the 113 patients in both LEOPOLD trials, 40 (35.4%) patients received rFVIII-FS prophylaxis pre-study and had data available for pre-study total ABR. In LEOPOLD I Part B (n = 22, 35.5%), median (Q1; Q3) total ABR decreased from 2.5 (0.0; 9.0) pre-study to 1.0 (0.0; 6.8), and from 1.0 (0.0; 6.0) pre-study to 0.0 (0.0; 6.02) in LEOPOLD Kids Part A (n = 18, 35.3%). Octocog alfa was well tolerated, and no patients had drug-related serious AEs or inhibitors.Conclusion: Treatment with octocog alfa prophylaxis appeared to have a favorable risk–benefit profile compared with rFVIII-FS and thus could be an effective and improved alternative strategy for individualized treatment for children, adolescent and adult patients with severe hemophilia A currently on rFVIII-FS treatment.Keywords: FVIII, hemophilia A, prophylaxis, recombinant proteins, octocog alfa |
| first_indexed | 2024-03-13T01:49:56Z |
| format | Article |
| id | doaj.art-d64314b94d4447dba917099f0a144fec |
| institution | Directory Open Access Journal |
| issn | 1179-2736 |
| language | English |
| last_indexed | 2024-03-13T01:49:56Z |
| publishDate | 2023-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Blood Medicine |
| spelling | doaj.art-d64314b94d4447dba917099f0a144fec2023-07-02T19:49:19ZengDove Medical PressJournal of Blood Medicine1179-27362023-06-01Volume 1437938884295Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical TrialsKenet GMoulton TWicklund BMAhuja SPEscobar MMahlangu JGili Kenet,1,2 Thomas Moulton,3 Brian M Wicklund,4 Sanjay P Ahuja,5 Miguel Escobar,6 Johnny Mahlangu7 1National Hemophilia Center, Sheba Medical Center, Tel HaShomer, Israel; 2The Amalia Biron Thrombosis Research Institute, Tel Aviv University, Tel Aviv, Israel; 3Bayer, Whippany, NJ, USA; 4Children’s Mercy-Kansas City, Kansas City, MO, USA; 5Rainbow Babies & Children’s Hospital, Cleveland, OH, USA; 6University of Texas Health Science Center, Houston, TX, USA; 7Hemophilia Comprehensive Care Center, Faculty of Health Sciences, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand, and National Health Laboratory Service, Johannesburg, South AfricaCorrespondence: Gili Kenet, Amalia Biron Thrombosis Research Institute, Tel Aviv University, Tel HaShomer, 52621, Israel, Tel +972-3-5307356, Fax +972-3-5351806, Email Gili.kenet@sheba.health.gov.ilIntroduction: Previous clinical trials established the efficacy and safety of sucrose-formulated recombinant factor (F) VIII (rFVIII-FS/Kogenate FS®/Helixate FS®) and octocog alfa (BAY 81– 8973/Kovaltry®; LEOPOLD trials).Aim: To report the results of a post hoc subgroup analysis assessing efficacy and safety outcomes in patients with hemophilia A who were receiving rFVIII-FS prior to enrolling into the LEOPOLD I Part B and LEOPOLD Kids Part A clinical trials and switching to octocog alfa.Methods: LEOPOLD I Part B (NCT01029340) and LEOPOLD Kids Part A (NCT01311648) were octocog alfa Phase 3, multinational, open-label studies in patients with severe hemophilia A aged 12– 65 years and ≤ 12 years, respectively. Annualized bleeding rate (ABR) was the efficacy endpoint for both studies. Safety endpoints included adverse events (AEs) and development of FVIII inhibitors.Results: Of the 113 patients in both LEOPOLD trials, 40 (35.4%) patients received rFVIII-FS prophylaxis pre-study and had data available for pre-study total ABR. In LEOPOLD I Part B (n = 22, 35.5%), median (Q1; Q3) total ABR decreased from 2.5 (0.0; 9.0) pre-study to 1.0 (0.0; 6.8), and from 1.0 (0.0; 6.0) pre-study to 0.0 (0.0; 6.02) in LEOPOLD Kids Part A (n = 18, 35.3%). Octocog alfa was well tolerated, and no patients had drug-related serious AEs or inhibitors.Conclusion: Treatment with octocog alfa prophylaxis appeared to have a favorable risk–benefit profile compared with rFVIII-FS and thus could be an effective and improved alternative strategy for individualized treatment for children, adolescent and adult patients with severe hemophilia A currently on rFVIII-FS treatment.Keywords: FVIII, hemophilia A, prophylaxis, recombinant proteins, octocog alfahttps://www.dovepress.com/switching-from-sucrose-formulated-rfviii-to-octocog-alfa-bay-81-8973-p-peer-reviewed-fulltext-article-JBMfviiihemophilia aprophylaxisrecombinant proteinsoctocog alfa |
| spellingShingle | Kenet G Moulton T Wicklund BM Ahuja SP Escobar M Mahlangu J Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials Journal of Blood Medicine fviii hemophilia a prophylaxis recombinant proteins octocog alfa |
| title | Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials |
| title_full | Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials |
| title_fullStr | Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials |
| title_full_unstemmed | Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials |
| title_short | Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials |
| title_sort | switching from sucrose formulated rfviii to octocog alfa bay 81 8973 prophylaxis improves bleed outcomes in the leopold clinical trials |
| topic | fviii hemophilia a prophylaxis recombinant proteins octocog alfa |
| url | https://www.dovepress.com/switching-from-sucrose-formulated-rfviii-to-octocog-alfa-bay-81-8973-p-peer-reviewed-fulltext-article-JBM |
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