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Fitusiran appears to promote hemostasis and reduce the frequency of bleeding in patients with hemophilia. In a phase I trial of the investigational agent, breakthrough bleeds were treated effectively and safely with replacement factor or bypassing agent.
Bleed events were rare among patients achieving target antithrombin lowering of greater than 75% on fitusiran. Those that did occur were treated with factor concentrates, including recombinant Factor VIII or recombinant Factor IX, or with bypassing agents, including recombinant Factor VIIa or activated prothrombin complex–concentrates, Savita Rangarajan, MD, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
The study included 41 patients with hemophilia A or B – 25 patients with inhibitors and 16 without inhibitors – who received either 50 mg or 80 mg of fitusiran. Early multiple ascending dose–cohorts received weekly subcutaneous dosing, and later cohorts received monthly dosing. All patients tolerated treatment well, with no serious adverse events related to the study drug. No thromboembolic events occurred, and the majority of adverse events were mild or moderate in severity, she noted.
Among patients with inhibitors, eight bleeds occurred in five patients with hemophilia A who were treated with Factor VIII, and three bleeds occurred in two patients with hemophilia B who were treated with Factor IX. Among those without inhibitors, six bleeds occurred in three patients treated with activated prothrombin complex–concentrates, and four occurred in three patients treated with recombinant Factor VIIa, said Dr. Rangarajan of Hampshire Hospitals NHS Foundation Trust, Basingstoke, England.
The ranges of factor replacement used per injection were 7-32 IU/kg of Factor VIII and 7-43 IU/kg of Factor IX.
The ranges of bypassing agents used per injection were 14-75 U/kg of activated prothrombin complex–concentrates (mean, 2.2 administrations per bleed) and 93-133 μg/kg of recombinant Factor VIIa (mean, 1.5 administrations per bleed), she said.
Doses of the factor concentrates and bypassing agents used were at or below those recommended by the World Federation of Hemophilia.
This phase I study of fitusiran, which targets and lowers antithrombin to improve thrombin generation and promote hemostasis in patients with hemophilia, is being conducted in four parts: Part A with healthy volunteers, parts B and C with patients with moderate to severe hemophilia A or B, and part D with patients with hemophilia A or B with inhibitors.
Findings from the current exploratory analysis of the data are encouraging as they demonstrate good treatment effect in the absence of identified safety concerns, Dr. Rangarajan said, noting that fitusiran should advance to pivotal studies in 2017 and that data on bleed management from a phase I and phase II open label extension will guide protocol on bleed management in phase III.
Dr. Rangarajan has received grant or research support from Alnylam Pharmaceuticals, BioMarin Pharmaceutical, Novo Nordisk, Pfizer, and Shire.
Fitusiran appears to promote hemostasis and reduce the frequency of bleeding in patients with hemophilia. In a phase I trial of the investigational agent, breakthrough bleeds were treated effectively and safely with replacement factor or bypassing agent.
Bleed events were rare among patients achieving target antithrombin lowering of greater than 75% on fitusiran. Those that did occur were treated with factor concentrates, including recombinant Factor VIII or recombinant Factor IX, or with bypassing agents, including recombinant Factor VIIa or activated prothrombin complex–concentrates, Savita Rangarajan, MD, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
The study included 41 patients with hemophilia A or B – 25 patients with inhibitors and 16 without inhibitors – who received either 50 mg or 80 mg of fitusiran. Early multiple ascending dose–cohorts received weekly subcutaneous dosing, and later cohorts received monthly dosing. All patients tolerated treatment well, with no serious adverse events related to the study drug. No thromboembolic events occurred, and the majority of adverse events were mild or moderate in severity, she noted.
Among patients with inhibitors, eight bleeds occurred in five patients with hemophilia A who were treated with Factor VIII, and three bleeds occurred in two patients with hemophilia B who were treated with Factor IX. Among those without inhibitors, six bleeds occurred in three patients treated with activated prothrombin complex–concentrates, and four occurred in three patients treated with recombinant Factor VIIa, said Dr. Rangarajan of Hampshire Hospitals NHS Foundation Trust, Basingstoke, England.
The ranges of factor replacement used per injection were 7-32 IU/kg of Factor VIII and 7-43 IU/kg of Factor IX.
The ranges of bypassing agents used per injection were 14-75 U/kg of activated prothrombin complex–concentrates (mean, 2.2 administrations per bleed) and 93-133 μg/kg of recombinant Factor VIIa (mean, 1.5 administrations per bleed), she said.
Doses of the factor concentrates and bypassing agents used were at or below those recommended by the World Federation of Hemophilia.
This phase I study of fitusiran, which targets and lowers antithrombin to improve thrombin generation and promote hemostasis in patients with hemophilia, is being conducted in four parts: Part A with healthy volunteers, parts B and C with patients with moderate to severe hemophilia A or B, and part D with patients with hemophilia A or B with inhibitors.
Findings from the current exploratory analysis of the data are encouraging as they demonstrate good treatment effect in the absence of identified safety concerns, Dr. Rangarajan said, noting that fitusiran should advance to pivotal studies in 2017 and that data on bleed management from a phase I and phase II open label extension will guide protocol on bleed management in phase III.
Dr. Rangarajan has received grant or research support from Alnylam Pharmaceuticals, BioMarin Pharmaceutical, Novo Nordisk, Pfizer, and Shire.
Fitusiran appears to promote hemostasis and reduce the frequency of bleeding in patients with hemophilia. In a phase I trial of the investigational agent, breakthrough bleeds were treated effectively and safely with replacement factor or bypassing agent.
Bleed events were rare among patients achieving target antithrombin lowering of greater than 75% on fitusiran. Those that did occur were treated with factor concentrates, including recombinant Factor VIII or recombinant Factor IX, or with bypassing agents, including recombinant Factor VIIa or activated prothrombin complex–concentrates, Savita Rangarajan, MD, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
The study included 41 patients with hemophilia A or B – 25 patients with inhibitors and 16 without inhibitors – who received either 50 mg or 80 mg of fitusiran. Early multiple ascending dose–cohorts received weekly subcutaneous dosing, and later cohorts received monthly dosing. All patients tolerated treatment well, with no serious adverse events related to the study drug. No thromboembolic events occurred, and the majority of adverse events were mild or moderate in severity, she noted.
Among patients with inhibitors, eight bleeds occurred in five patients with hemophilia A who were treated with Factor VIII, and three bleeds occurred in two patients with hemophilia B who were treated with Factor IX. Among those without inhibitors, six bleeds occurred in three patients treated with activated prothrombin complex–concentrates, and four occurred in three patients treated with recombinant Factor VIIa, said Dr. Rangarajan of Hampshire Hospitals NHS Foundation Trust, Basingstoke, England.
The ranges of factor replacement used per injection were 7-32 IU/kg of Factor VIII and 7-43 IU/kg of Factor IX.
The ranges of bypassing agents used per injection were 14-75 U/kg of activated prothrombin complex–concentrates (mean, 2.2 administrations per bleed) and 93-133 μg/kg of recombinant Factor VIIa (mean, 1.5 administrations per bleed), she said.
Doses of the factor concentrates and bypassing agents used were at or below those recommended by the World Federation of Hemophilia.
This phase I study of fitusiran, which targets and lowers antithrombin to improve thrombin generation and promote hemostasis in patients with hemophilia, is being conducted in four parts: Part A with healthy volunteers, parts B and C with patients with moderate to severe hemophilia A or B, and part D with patients with hemophilia A or B with inhibitors.
Findings from the current exploratory analysis of the data are encouraging as they demonstrate good treatment effect in the absence of identified safety concerns, Dr. Rangarajan said, noting that fitusiran should advance to pivotal studies in 2017 and that data on bleed management from a phase I and phase II open label extension will guide protocol on bleed management in phase III.
Dr. Rangarajan has received grant or research support from Alnylam Pharmaceuticals, BioMarin Pharmaceutical, Novo Nordisk, Pfizer, and Shire.
Key clinical point:
Major finding: 21 bleeds occurred in 13 patients, and all were treated effectively and safely.
Data source: An exploratory analysis of data from a four-part phase I trial.
Disclosures: Dr. Rangarajan has received grant or research support from Alnylam Pharmaceuticals, BioMarin Pharmaceutical, Novo Nordisk, Pfizer, and Shire.