Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study
The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (s...
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| Veröffentlicht in: | Thrombosis and haemostasis 2012-11, Vol.108 (5), p.913-922 |
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| creator | Powell, Jerry Martinowitz, Uri Windyga, Jerzy Di Minno, Giovanni Hellmann, Andrzej Pabinger, Ingrid Maas Enriquez, Monika Schwartz, Lawrence Ingerslev, Jørgen |
| description | The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating |
| doi_str_mv | 10.1160/TH12-03-0188 |
| format | Article |
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A randomised, active-controlled, double-blind study</title><source>MEDLINE</source><source>Thieme Connect Journals</source><creator>Powell, Jerry ; Martinowitz, Uri ; Windyga, Jerzy ; Di Minno, Giovanni ; Hellmann, Andrzej ; Pabinger, Ingrid ; Maas Enriquez, Monika ; Schwartz, Lawrence ; Ingerslev, Jørgen</creator><creatorcontrib>Powell, Jerry ; Martinowitz, Uri ; Windyga, Jerzy ; Di Minno, Giovanni ; Hellmann, Andrzej ; Pabinger, Ingrid ; Maas Enriquez, Monika ; Schwartz, Lawrence ; Ingerslev, Jørgen ; LipLong Study Investigators ; the LipLong Study Investigators</creatorcontrib><description>The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. 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A randomised, active-controlled, double-blind study</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Chemistry, Pharmaceutical</subject><subject>Delayed-Action Preparations</subject><subject>Double-Blind Method</subject><subject>Drug Administration Schedule</subject><subject>Factor VIII - administration & dosage</subject><subject>Factor VIII - adverse effects</subject><subject>Hemophilia A - drug therapy</subject><subject>Hemorrhage - prevention & control</subject><subject>Humans</subject><subject>Liposomes - administration & dosage</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polyethylene Glycols - administration & dosage</subject><subject>Solvents</subject><subject>Sucrose - administration & dosage</subject><subject>Sucrose - adverse effects</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMlOwzAURS0EglLYsUb-gBrsDI6zLBWFSpVYMAhWkUfVkMSR7QL5Lz6QRGVYvauno_ueDgBnBF8QQvHlwy1JEE4RJoztgUmS0wJRVj7vgwlOM4xokuVH4DiEV4wJzcr8EBwlKSZZQcgEfF0bYyWXPeStgoEbHXvoDOy86zZ9zT9tgB82bqBrpUYfWr_VPbyav8CiRFnJMJSu6bjXakfFjbf_nF8-rVYrtLyHtoUbrpuh09aWwznseLS6jeFiyH447RobtJpBLqN910i6NnpX1-NKua2oNRK1HT-MW9WfgAPD66BPf-YUPC6vHxa3aH13s1rM10gSmkaUpYKbQhPDhUpEQgnTlHLMTKaEICLPB4qRXDHFZIJ5ojARpS6KAWOF4iadgtmuV3oXgtem6rxtuO8rgqtRfjXKr3BajfIH_HyHd1vRaPUH_9pOvwGMCoFX</recordid><startdate>201211</startdate><enddate>201211</enddate><creator>Powell, Jerry</creator><creator>Martinowitz, Uri</creator><creator>Windyga, Jerzy</creator><creator>Di Minno, Giovanni</creator><creator>Hellmann, Andrzej</creator><creator>Pabinger, Ingrid</creator><creator>Maas Enriquez, Monika</creator><creator>Schwartz, Lawrence</creator><creator>Ingerslev, Jørgen</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201211</creationdate><title>Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study</title><author>Powell, Jerry ; Martinowitz, Uri ; Windyga, Jerzy ; Di Minno, Giovanni ; Hellmann, Andrzej ; Pabinger, Ingrid ; Maas Enriquez, Monika ; Schwartz, Lawrence ; Ingerslev, Jørgen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c163t-43baf7e1fabd2b2618e66a08f4dbb1b55163815d8d8c20a2d01b9e778e687daf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Chemistry, Pharmaceutical</topic><topic>Delayed-Action Preparations</topic><topic>Double-Blind Method</topic><topic>Drug Administration Schedule</topic><topic>Factor VIII - administration & dosage</topic><topic>Factor VIII - adverse effects</topic><topic>Hemophilia A - drug therapy</topic><topic>Hemorrhage - prevention & control</topic><topic>Humans</topic><topic>Liposomes - administration & dosage</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Polyethylene Glycols - administration & dosage</topic><topic>Solvents</topic><topic>Sucrose - administration & dosage</topic><topic>Sucrose - adverse effects</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Powell, Jerry</creatorcontrib><creatorcontrib>Martinowitz, Uri</creatorcontrib><creatorcontrib>Windyga, Jerzy</creatorcontrib><creatorcontrib>Di Minno, Giovanni</creatorcontrib><creatorcontrib>Hellmann, Andrzej</creatorcontrib><creatorcontrib>Pabinger, Ingrid</creatorcontrib><creatorcontrib>Maas Enriquez, Monika</creatorcontrib><creatorcontrib>Schwartz, Lawrence</creatorcontrib><creatorcontrib>Ingerslev, Jørgen</creatorcontrib><creatorcontrib>LipLong Study Investigators</creatorcontrib><creatorcontrib>the LipLong Study Investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Powell, Jerry</au><au>Martinowitz, Uri</au><au>Windyga, Jerzy</au><au>Di Minno, Giovanni</au><au>Hellmann, Andrzej</au><au>Pabinger, Ingrid</au><au>Maas Enriquez, Monika</au><au>Schwartz, Lawrence</au><au>Ingerslev, Jørgen</au><aucorp>LipLong Study Investigators</aucorp><aucorp>the LipLong Study Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2012-11</date><risdate>2012</risdate><volume>108</volume><issue>5</issue><spage>913</spage><epage>922</epage><pages>913-922</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><abstract>The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.</abstract><cop>Germany</cop><pmid>23014711</pmid><doi>10.1160/TH12-03-0188</doi><tpages>10</tpages></addata></record> |
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| identifier | ISSN: 0340-6245 |
| ispartof | Thrombosis and haemostasis, 2012-11, Vol.108 (5), p.913-922 |
| issn | 0340-6245 2567-689X |
| language | eng |
| recordid | cdi_crossref_primary_10_1160_TH12_03_0188 |
| source | MEDLINE; Thieme Connect Journals |
| subjects | Adolescent Adult Chemistry, Pharmaceutical Delayed-Action Preparations Double-Blind Method Drug Administration Schedule Factor VIII - administration & dosage Factor VIII - adverse effects Hemophilia A - drug therapy Hemorrhage - prevention & control Humans Liposomes - administration & dosage Male Middle Aged Polyethylene Glycols - administration & dosage Solvents Sucrose - administration & dosage Sucrose - adverse effects Treatment Outcome Young Adult |
| title | Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study |
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