HEMLIBRA Rx

Hemophilia A without FVIII Inhibitors

The approval was based on data from two phase 3 clinical trials: HAVEN 3 and HAVEN 4. 

In the HAVEN 3 study (N=89), patients 12 years of age and older with hemophilia A without factor VIII inhibitors who received Hemlibra prophylaxis 1.5 mg/kg once weekly or 3 mg/kg every 2 weeks experienced the following reductions in annualized bleed rates (ABR) compared with those who received no prophylaxis, respectively:

• Treated Bleeds: 96% (95% CI, 92.5-98.0; P <.0001) and 97% (95% CI, 93.4-98.3; P <.0001)

• All Bleeds: 95% (95% CI, 90.1-97; P <.0001) and 94% (95% CI, 89.7-97; P <.0001)

• Treated Spontaneous Bleeds: 94% (95% CI, 84.9-97.5; P <.0001) and 98% (95% CI, 94.4-99.4; P <.0001)

• Treated Joint Bleeds: 96% (95% CI, 91.5-98.1; P <.0001) and 97% (95% CI, 93-98.5; P <.0001)

• Treated Target Joint Bleeds: 95% (95% CI, 85.7-98.4; P <.0001) and 95% (95% CI, 85.3-98.2; P <.0001)

In the HAVEN 3 intra-patient analysis, Hemlibra prophylaxis achieved a statistically significant 68% reduction in bleed rate for treated bleeds compared with previous FVIII prophylaxis collected in the NIS prior to enrollment (P <.0001). 

In the HAVEN 4 study, Hemlibra prophylaxis every 4 weeks (N=41) was associated with clinically meaningful control of bleeding in patients with hemophilia A without factor VIII inhibitors (ABR: 2.6; 95% CI: 1.5, 4.7).

Hemophilia A with FVIII Inhibitors

The approval of Hemlibra for routine prophylaxis in patients with hemophilia A with FVIII inhibitors was based on data from 3 clinical trials: [adult and adolescent studies (HAVEN 1 and HAVEN 4) and a pediatric study (HAVEN 2)].

In the HAVEN 1 study (N=89), patients 12 years of age and older with hemophilia A with factor VIII inhibitors who received Hemlibra prophylaxis 1.5 mg/kg once weekly experienced the following reductions in annualized bleed rates (ABR) compared with those who received no prophylaxis:

• Treated Bleeds: 87% (95% CI, 72.3-94.3; P <.0001)

• All Bleeds: 80% (95% CI, 62.5-89.8; P <.0001)

• Treated Spontaneous Bleeds: 92% (95% CI, 84.6-96.3; P <.0001)

• Treated Joint Bleeds: 89% (48-97.5; P =.0050)

• Treated Targeted Joint Bleeds: 95% (95% CI, 77.3-99.1; P =.0002)

In the HAVEN 1 intra-patient analysis, Hemlibra prophylaxis achieved a statistically significant 79% reduction in bleed rate for treated bleeds compared with previous bypassing agent prophylaxis collected in the NIS prior to enrollment (P =.0003).

In the HAVEN 2 study, patients less than 12 years of age or patients 12 to 17 years of age weighing less than 40kg were enrolled who had hemophilia A with FVIII inhibitors. At the time of interim analysis, there were 59 pediatric patients less than 12 years of age, including 38 who were 6 to less than 12 years, 17 who were 2 to less than 6 years, and 4 who were less than 2 years. Patients who received Hemlibra prophylaxis 1.5 mg/kg once weekly had the following ABRs:

• Treated Bleeds: 0.3 (95% CI, 0.1-0.5)

• All Bleeds: 3.8 (95% CI, 2.2-6.5)

• Treated Spontaneous Bleeds: 0 (95% CI, 0-0.2)

• Treated Joint Bleeds: 0.2 (95% CI, 0.1-0.4)

• Treated Targeted Joint Bleeds: 0.1 (95% CI, 0-0.7)

In the HAVEN 2 intra-patient analysis, 18 pediatric patients who had participated in the NIS had an ABR for treated bleeds of 19.8 (95% CI, 15.3-25.7]) on previous bypassing agent treatment (prophylactic treatment in 15 patients and on-demand treatment for 3 patients). Hemlibra prophylaxis resulted in an ABR for treated bleeds of 0.4 (95% CI, 0.2-0.9]) based on negative binomial regression, corresponding to a 98% reduction in bleed rate. On Hemlibra prophylaxis, 14 patients (77.8%) had zero treated bleeds. 

In the HAVEN 4 study, 41 patients 12 years of age and older weighing at least 40 kg were enrolled who had hemophilia A with or without FVIII inhibitors and previously received either episodic (on demand) or prophylactic treatment with FVIII or bypassing agents. Patients received Hemlibra prophylaxis at 3 mg/kg once weekly for the first 4 weeks then 6 mg/kg once every 4 weeks thereafter. Treatment with Hemlibra prophylaxis every 4 weeks was associated with clinically meaningful control of bleeding in patients with hemophilia A with factor VIII inhibitors and without factor VIII inhibitors (ABR: 2.4; 95% CI, 1.4-4.3).