There were 130 treatment instances of aPCC in 37 patients taking HEMLIBRA. Cases of TMA and TEs were reported when on average a cumulative amount of >100 U/kg/24 hours of aPCC was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis.1
Duration of aPCC (hours) | Average aPCC daily dose (U/kg/24 hours)1 | ||
---|---|---|---|
<50 | 50-100 | >100 | |
<24 | 11 | 76 | 18 |
24-48 | 0 | 6 | 3 1 TE |
>48 | 1 | 5 | 10 3 TMA 1 TE |
Five of the 13 treatment instances reported TMA or thrombotic events when using cumulative amounts of aPCC averaging >100 U/kg/24 hours for ≥24 hours1
HAVEN 3 and HAVEN 4: 274 treatment instances of FVIII in 83 patients taking HEMLIBRA3,30
Duration of FVIII (hours) |
Average FVIII daily dose (IU/kg/24 hours) | |
---|---|---|
<50 | ≥50 | |
<24 | 188 | 41 |
24-<48 | 22 | 6 |
≥48 | 13 | 4 |
Clinical experience was limited and of relatively short duration (median treatment exposure was up to 31 weeks for HAVEN 3 and 26 weeks for HAVEN 4) and cannot exclude the possibility of occurrence of events with FVIII therapy when taking HEMLIBRA3
HAVEN 1 and HAVEN 2: 256 treatment instances of rFVIIa in 66 patients taking HEMLIBRA3
Duration of rFVIIa (hours) |
Average rFVIIa daily dose (µg/kg/24 hours) | |||
---|---|---|---|---|
<90 | 90-180 | 181-270 | >270 | |
<24 | 44 | 66 | 58 | 24 |
24-<48 | 2 | 10 | 17 |
8 |
≥48 | 0 | 2 | 9 | 16 |
Clinical experience was limited and of relatively short duration (median treatment exposure was 42 weeks for HAVEN 1, 29 weeks for HAVEN 2) and cannot exclude the possibility of occurrence of events with rFVIIa therapy when taking HEMLIBRA3
Retrospective data on unplanned surgeries with HEMLIBRA in HAVEN 1–4 are available.17
Advise the patient and/or caregiver that prophylactic use of FVIII may be continued for the first week of HEMLIBRA prophylaxis. Discuss the use of BPAs or FVIII with the patient and/or caregiver prior to starting HEMLIBRA prophylaxis.
Advise the patient and/or caregiver that prophylactic use of FVIII may be continued for the first week of HEMLIBRA prophylaxis. Discuss the use of BPAs or FVIII with the patient and/or caregiver prior to starting HEMLIBRA prophylaxis.
Advise the patient and/or caregiver that prophylactic use of FVIII may be continued for the first week of HEMLIBRA prophylaxis. Discuss the use of BPAs or FVIII with the patient and/or caregiver prior to starting HEMLIBRA prophylaxis.
*NBDF's MASAC recommendations state that all patients on HEMLIBRA prophylaxis who receive aPCC for breakthrough bleeding for more than 24 hrs should do so in close contact with their healthcare providers. Patients should be evaluated for any symptoms that could indicate a thromboembolic event (with a high level of suspicion for atypical sites, such as cerebral sinus venous thrombosis), and have clinical evaluation for hypertension and proteinuria to look for evidence for TMA. Laboratory monitoring should include complete blood count, peripheral blood smear analysis to look for schistocytes, D-dimer, prothrombin fragment F1+2 (if available), haptoglobin, bilirubin, serum creatinine, LDH and troponin. Consider daily laboratory monitoring for patients who require aPCC beyond the recommended dose and duration guidelines.15
aPCC=activated prothrombin complex concentrate; BPA=bypassing agent; FVIII=factor VIII; LDH=lactate dehydrogenase; rFVIIa=activated recombinant factor VII; SAE=serious adverse event; TE=thrombotic event; TMA=thrombotic microangiopathy.
Learn more about HEMLIBRA clinical trial results across various patient populations.
To learn more about HEMLIBRA, contact your local representative.
HEMLIBRA package insert. South San Francisco, CA: Genentech, Inc.; 2024.
HEMLIBRA package insert. South San Francisco, CA: Genentech, Inc.; 2024.
FDA Approves Genentech’s HEMLIBRA (emicizumab-kxwh) for Hemophilia A Without Factor VIII Inhibitors. Genentech Press Release. South San Francisco, CA: Genentech; October 4, 2018.
FDA Approves Genentech’s HEMLIBRA (emicizumab-kxwh) for Hemophilia A Without Factor VIII Inhibitors. Genentech Press Release. South San Francisco, CA: Genentech; October 4, 2018.
Data on File. Genentech, Inc.
Data on File. Genentech, Inc.
Young G, Liesner R, Chang T, et al. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019;134(24):2127-2138. doi:10.1182/blood.2019001869
Young G, Liesner R, Chang T, et al. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019;134(24):2127-2138. doi:10.1182/blood.2019001869
Young G, Sidonio R, Oldenburg J, et al. Efficacy/safety in children on 2/4-weekly emicizumab prophylaxis: 52-week outcomes in HAVEN 2. Presented at the American Society of Pediatric Hematology/Oncology (ASPHO) Conference; May 4-7, 2022; Pittsburgh, Pennsylvania.
Young G, Sidonio R, Oldenburg J, et al. Efficacy/safety in children on 2/4-weekly emicizumab prophylaxis: 52-week outcomes in HAVEN 2. Presented at the American Society of Pediatric Hematology/Oncology (ASPHO) Conference; May 4-7, 2022; Pittsburgh, Pennsylvania.
Shima M, Nagao A, Taki M, et al. Long-term safety and efficacy of emicizumab for up to 5.8 years and patients’ perceptions of symptoms and daily life: A phase 1/2 study in patients with severe haemophilia A. Haemophilia. 2021;27(1):81-89. doi:10.1111/hae.14205
Shima M, Nagao A, Taki M, et al. Long-term safety and efficacy of emicizumab for up to 5.8 years and patients’ perceptions of symptoms and daily life: A phase 1/2 study in patients with severe haemophilia A. Haemophilia. 2021;27(1):81-89. doi:10.1111/hae.14205
Shima M, Nogami K, Nagami S, et al. A multicentre, open-label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors. Haemophilia. 2019;25(6):979-987. doi:10.1111/hae.13848
Shima M, Nogami K, Nagami S, et al. A multicentre, open-label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors. Haemophilia. 2019;25(6):979-987. doi:10.1111/hae.13848
Négrier C, Mahlangu J, Lehle M, et al. Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study. Lancet Haematol. 2023;10(3):e168-e177. doi:10.1016/S2352-3026(22)00377-5
Négrier C, Mahlangu J, Lehle M, et al. Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study. Lancet Haematol. 2023;10(3):e168-e177. doi:10.1016/S2352-3026(22)00377-5
Pipe SW, Collins P, Dhalluin C, et al. Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b open-label trial. Blood. 2024;143(14):1355-1364. doi:10.1182/blood.2023021832
Pipe SW, Collins P, Dhalluin C, et al. Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b open-label trial. Blood. 2024;143(14):1355-1364. doi:10.1182/blood.2023021832
Jiménez-Yuste V, Peyvandi F, Klamroth R, et al. Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single-arm study (STASEY). Res Pract Thromb Haemost. 2022;6(8):e12837. doi:10.1002/rth2.12837
Jiménez-Yuste V, Peyvandi F, Klamroth R, et al. Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single-arm study (STASEY). Res Pract Thromb Haemost. 2022;6(8):e12837. doi:10.1002/rth2.12837
Efficacy, safety, and pharmacokinetic study of prophylactic emicizumab versus no prophylaxis in hemophilia A participants (HAVEN 5). Clinicaltrials.gov identifier: NCT03315455. Updated September 25, 2024. Accessed November 19, 2024. https://clinicaltrials.gov/ct2/show/NCT03315455.
Efficacy, safety, and pharmacokinetic study of prophylactic emicizumab versus no prophylaxis in hemophilia A participants (HAVEN 5). Clinicaltrials.gov identifier: NCT03315455. Updated September 25, 2024. Accessed November 19, 2024. https://clinicaltrials.gov/ct2/show/NCT03315455.
Kitazawa T, Esaki K, Tachibana T, et al. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost. 2017:117(7):1348-1357. doi:10.1160/TH17-01-0030
Kitazawa T, Esaki K, Tachibana T, et al. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost. 2017:117(7):1348-1357. doi:10.1160/TH17-01-0030
Callaghan MU, Negrier C, Paz-Priel I, et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Supplement. Blood. 2021;137(16):2231-2242. doi:10.1182/blood.2020009217
Callaghan MU, Negrier C, Paz-Priel I, et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Supplement. Blood. 2021;137(16):2231-2242. doi:10.1182/blood.2020009217
Callaghan MU, Negrier C, Paz-Priel I, et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood. 2021;137(16):2231-2242. doi:10.1182/blood.2020009217
Callaghan MU, Negrier C, Paz-Priel I, et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood. 2021;137(16):2231-2242. doi:10.1182/blood.2020009217
National Bleeding Disorders Foundation. MASAC Document 268: Recommendation on the use and management of emicizumab-kxwh (HEMLIBRA) for hemophilia A with and without inhibitors. April 27, 2022; New York, NY.
National Bleeding Disorders Foundation. MASAC Document 268: Recommendation on the use and management of emicizumab-kxwh (HEMLIBRA) for hemophilia A with and without inhibitors. April 27, 2022; New York, NY.
McCary I, Guelcher C, Kuhn J, et al. Real-world use of emicizumab in patients with haemophilia A: bleeding outcomes and surgical procedures. Haemophilia. 2020;26(4):631-636. doi:10.1111/hae.14005
McCary I, Guelcher C, Kuhn J, et al. Real-world use of emicizumab in patients with haemophilia A: bleeding outcomes and surgical procedures. Haemophilia. 2020;26(4):631-636. doi:10.1111/hae.14005
Kruse-Jarres R, Peyvandi F, Oldenburg J, et al. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Blood. 2022;6(24):6140-6150. doi: 10.1182/bloodadvances.2022007458
Kruse-Jarres R, Peyvandi F, Oldenburg J, et al. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Blood. 2022;6(24):6140-6150. doi: 10.1182/bloodadvances.2022007458
Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809-818. doi:10.1056/NEJMoa1703068
Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809-818. doi:10.1056/NEJMoa1703068
Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. Supplement. N Engl J Med. 2017;377(9):809-818. doi:10.1056/NEJMoa1703068
Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. Supplement. N Engl J Med. 2017;377(9):809-818. doi:10.1056/NEJMoa1703068
Ebbert PT, Xavier F, Seaman CD, Ragni MV. Emicizumab prophylaxis in patients with haemophilia A with and without inhibitors. Haemophilia. 2020;26(1):41-46. doi:10.1111/hae.13877
Ebbert PT, Xavier F, Seaman CD, Ragni MV. Emicizumab prophylaxis in patients with haemophilia A with and without inhibitors. Haemophilia. 2020;26(1):41-46. doi:10.1111/hae.13877
Hassan E, Jonathan L, Jayashree M. Real-world experience on the tolerability and safety of emicizumab prophylaxis in paediatric patients with severe haemophilia A with and without FVIII inhibitors. Haemophilia. 2021;27(6):e698-e703. doi:10.1111/hae.14432
Hassan E, Jonathan L, Jayashree M. Real-world experience on the tolerability and safety of emicizumab prophylaxis in paediatric patients with severe haemophilia A with and without FVIII inhibitors. Haemophilia. 2021;27(6):e698-e703. doi:10.1111/hae.14432
Schmitt C, Emrich T, Chebon S, et al. Low immunogenicity of emicizumab in persons with haemophilia A. Haemophilia. 2021;27(6):984-992. doi:10.1111/hae.14398
Schmitt C, Emrich T, Chebon S, et al. Low immunogenicity of emicizumab in persons with haemophilia A. Haemophilia. 2021;27(6):984-992. doi:10.1111/hae.14398
Mahlangu J, Jiménez-Yuste V, Ventriglia G, et al. Long-term outcomes with emicizumab in hemophilia A without inhibitors: results from the HAVEN 3 and 4 studies. Res Pract Thromb Haemost. 2024;8(2):102364. doi:10.1016/j.rpth.2024.102364
Mahlangu J, Jiménez-Yuste V, Ventriglia G, et al. Long-term outcomes with emicizumab in hemophilia A without inhibitors: results from the HAVEN 3 and 4 studies. Res Pract Thromb Haemost. 2024;8(2):102364. doi:10.1016/j.rpth.2024.102364
Di Minno A, Spadarella G, Nardone A, et al. Attempting to remedy sub-optimal medication adherence in haemophilia: the rationale for repeated ultrasound visualisations of the patient’s joint status. Blood Rev. 2019;33:106-116. doi:10.1016/j.blre.2018.08.003
Di Minno A, Spadarella G, Nardone A, et al. Attempting to remedy sub-optimal medication adherence in haemophilia: the rationale for repeated ultrasound visualisations of the patient’s joint status. Blood Rev. 2019;33:106-116. doi:10.1016/j.blre.2018.08.003
Schrijvers LH, Schuurmans MJ, Fischer K. Promoting self-management and adherence during prophylaxis: evidence-based recommendations for haemophilia professionals. Haemophilia. 2016;22(4):499-506. doi:10.1111/hae.12904
Schrijvers LH, Schuurmans MJ, Fischer K. Promoting self-management and adherence during prophylaxis: evidence-based recommendations for haemophilia professionals. Haemophilia. 2016;22(4):499-506. doi:10.1111/hae.12904
Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535-544. doi:10.1056/NEJMoa067659
Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535-544. doi:10.1056/NEJMoa067659
National Bleeding Disorders Foundation. MASAC Document 267: MASAC Recommendation Concerning Prophylaxis for Hemophilia A and B with and without Inhibitors. April 27, 2022; New York, NY.
National Bleeding Disorders Foundation. MASAC Document 267: MASAC Recommendation Concerning Prophylaxis for Hemophilia A and B with and without Inhibitors. April 27, 2022; New York, NY.
Pipe S, Collins P, Dhalluin C, et al. Emicizumab Prophylaxis in Infants with Severe Hemophilia A without Factor VIII Inhibitors: Results from the Primary Analysis of the HAVEN 7 Study. Slide deck presented at: 65th ASH Annual Meeting; December 9-12, 2023; San Diego, California.
Pipe S, Collins P, Dhalluin C, et al. Emicizumab Prophylaxis in Infants with Severe Hemophilia A without Factor VIII Inhibitors: Results from the Primary Analysis of the HAVEN 7 Study. Slide deck presented at: 65th ASH Annual Meeting; December 9-12, 2023; San Diego, California.
Ljung R, de Kovel M, van den Berg HM on behalf of the PedNet study group. Primary prophylaxis in children with severe haemophilia A and B—Implementation over the last 20 years as illustrated in real-world data in the PedNet cohorts. Haemophilia. 2023;29(2):498-504. doi:10.1111/hae.14729
Ljung R, de Kovel M, van den Berg HM on behalf of the PedNet study group. Primary prophylaxis in children with severe haemophilia A and B—Implementation over the last 20 years as illustrated in real-world data in the PedNet cohorts. Haemophilia. 2023;29(2):498-504. doi:10.1111/hae.14729
Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med. 2018;379(9):811-822. doi:10.1056/NEJMoa1803550
Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med. 2018;379(9):811-822. doi:10.1056/NEJMoa1803550
HEMLIBRA Summary of Product Characteristics. Roche Registration Limited; 2022.
HEMLIBRA Summary of Product Characteristics. Roche Registration Limited; 2022.
Kruse-Jarres R, Peyvandi F, Oldenburg J, et al. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Supplementary materials. Blood Adv. 2022;6(24):6140-6150. doi:10.1182/bloodadvances.2022007458
Kruse-Jarres R, Peyvandi F, Oldenburg J, et al. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Supplementary materials. Blood Adv. 2022;6(24):6140-6150. doi:10.1182/bloodadvances.2022007458
HEMLIBRA Instructions For Use. Roche Registration Limited; 2022.
HEMLIBRA Instructions For Use. Roche Registration Limited; 2022.
Doyle GR, McCutcheon JA. Clinical Procedures for Safer Patient Care. Victoria, BC: BCcampus. 2015. Retrieved from https://opentextbc.ca/clinicalskills/
Doyle GR, McCutcheon JA. Clinical Procedures for Safer Patient Care. Victoria, BC: BCcampus. 2015. Retrieved from https://opentextbc.ca/clinicalskills/
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