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The European Commission has approved a full-length recombinant factor VIII product for the treatment and prevention of bleeding in hemophilia A patients of all ages.
The product, Kovaltry (formerly BAY 81-8973), will be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
The approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A.
The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.
LEOPOLD I
LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.
The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD II
LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).
The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD Kids
LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.
For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.
Safety results
For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.
The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.
The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).
None of the patients developed factor VIII inhibitors. 
The European Commission has approved a full-length recombinant factor VIII product for the treatment and prevention of bleeding in hemophilia A patients of all ages.
The product, Kovaltry (formerly BAY 81-8973), will be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
The approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A.
The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.
LEOPOLD I
LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.
The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD II
LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).
The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD Kids
LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.
For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.
Safety results
For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.
The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.
The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).
None of the patients developed factor VIII inhibitors.
The European Commission has approved a full-length recombinant factor VIII product for the treatment and prevention of bleeding in hemophilia A patients of all ages.
The product, Kovaltry (formerly BAY 81-8973), will be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
The approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A.
The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.
LEOPOLD I
LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.
The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD II
LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).
The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD Kids
LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.
For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.
Safety results
For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.
The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.
The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).
None of the patients developed factor VIII inhibitors.