SmPC

SmPC for Cablivi® caplacizumab 10 mg powder and solvent for solution for injection:

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Cablivi is indicated for the treatment of adults and adolescents of 12 years of age and older weighing at least 40 kg experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP), in conjunction with plasma exchange (PEX) + immunosuppression (IMS).2

CABLIVI is a humanised nanobody that rapidly binds to the A1 domain of von Willebrand factor, preventing the ULvWF factor mediated platelet adhesion that is characteristic of aTTP.

Cablivi (caplacizumab) is the first licensed disease-modifying treatment for aTTP.1

Cablivi plus PEX+IMS can help you achieve platelet normalisation in your patients with aTTP faster vs. PEX+IMS alone.2

The National Institute for Health and Care Excellence (NICE) has recommended the use of Cablivi in line with its full indication.1

Evidence

Efficacy

Maximise your efficacy in aTTP treatment

Cablivi has been assessed in two controlled Phase III clinical trials (Scully M, et al. 2019 and Coppo P, et al. 2021).3,4 Pooled analysis of the data from the Phase II TITAN5 and Phase III HERCULES3 trials was recently published by Peyvandi F, et al. 2021 in Blood Advances, confirming the findings from the other two studies in terms of mortality, refractory disease and safety data.6

  • Median time to normalisation of platelet count was significantly shorter in patients treated with Cablivi plus PEX+IMS vs. PEX+IMS alone (p=0.01).3

    Adapted from Scully M, et al. 2019.

    Patients were 1.55x more likely to achieve platelet normalisation and had a significantly reduced platelet normalisation time with Cablivi plus PEX+IMS at any given time point vs. PEX+IMS alone.2,3

  • Cablivi plus PEX+IMS recovered durable platelet count in 5 (4–6) days vs. 12 (6–17) days for PEX+IMS alone (p<0.001).4

    Adapted from Coppo P, et al. 2021.

    Cablivi plus PEX+IMS recovered durable platelet count 1.8x more rapidly than PEX+IMS alone.⁴

    No TTP-related deaths occurred in patients treated with CABLIVI plus PEX+IMS vs. 3 patients treated with PEX+IMS alone.

    CABLIVI plus PEX+IMS reduces the chance of exacerbation of aTTP by 67% vs. PEX+IMS alone (12% [9/72] vs. 38% [28/73], p<0.001).

    Pooled analysis of the Phase II and Phase III clinical trials further demonstrated Cablivi plus PEX+IMS prevents mortality and refractory disease in aTTP patients.⁶

    *1 patient treated with Cablivi plus PEX+IMS died during the treatment-free follow-up period. The cause of death was cerebral ischaemia and was assessed by the investigator as unrelated to treatment.3

    • Cablivi plus PEX+IMS significantly reduced the number of days in hospital vs. PEX+IMS alone by 4.5 days (9.9 days vs.14.4 days; P values not reported)2,3
    • Cablivi plus PEX+IMS (n=28) reduced the number of days in intensive care unit (ICU) vs. PEX+IMS alone (n=27) by 6.3 days (3.4) days [28/71] vs. 9.7 days [27/72]; P values not reported)2,3
    • Cablivi plus PEX+IMS reduced the days on PEX vs. PEX+IMS alone by 38% (3.6 days, 5.8 days vs. 9.4 days)2,3

    *1 patient withdrew from the trial.3

    British Society for Haematology (BHS) webinar: CABLIVI UK real-world experience

    Scully M, Cataland SR, Peyvandi F, et al.
    Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura.
    N Engl J Med. 2019;380(4):335–346.

    Coppo P, Bubenheim M, Axoulay E, et al.
    A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP.
    Blood. 2021;137(6):733–742.

    Peyvandi F, Cataland S, Scully M, et al.
    Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis.
    Blood Adv. 2021.5(8):2137–2141.

Cablivi plus PEX+IMS helps patients achieve a platelet response when they need it most.2–4

Safety

Cablivi’s safety profile has been investigated in controlled clinical trials and is consistent with its mechanism of action in aTTP.2

Bleeding events associated with Cablivi were generally self-limited, and all events in the Phase III clinical trial resolved, most without intervention2,3

Cablivi plus PEX+IMS had a lower discontinuation rate (7% [5/71]) vs. PEX+IMS alone (12.3% [9/73])3

‡1 patient withdrew from the trial.3

    The most frequent adverse reactions (very common ≥1/10) reported were epistaxis, headache, gingival bleeding, urticaria, pyrexia and fatigue.2,3

     

    Cablivi plus PEX+IMS
    (N=71)

    PEX+IMS alone
    (N=73)

    At least 1 treatment-emergent
    adverse event (TEAE)

    95.8% (68)

    90.3% (66)

    Epistaxis

    32.4% (23)

    2.7% (2)

    Gingival bleeding

    18.3% (13)

    1.4% (1)

    • In case of active, significant bleeding, treatment with Cablivi should be interrupted and only restarted upon the advice of a physician experienced in the management of thrombotic microangiopathies2
    • Close clinical monitoring and benefit/risk assessment must be completed for initiation or continuation of Cablivi treatment with anticoagulants/heparin as there have been no interaction studies evaluating the use of Cablivi with oral anticoagulants/high dose heparin2
    • In patients with underlying coagulopathies, the use of Cablivi must be accompanied by close clinical monitoring2
    • Patients undergoing surgery/dental procedures should be advised to inform their physician/dentist that they are using Cablivi and treatment should be stopped at least 7 days before the planned intervention2

Usage

Cablivi dosing schedule

Cablivi is administered by both intravenous (IV) and subcutaneous (SC) injection and should be initiated and supervised by physicians experienced in the management of patients with thrombotic microangiopathies.2

Mechanism of action

Cablivi is an innovative therapy designed to act on the underlying disease pathology of aTTP.2

Cablivi is a humanised nanobody that rapidly binds to the A1 domain of von Willebrand factor (vWF) preventing the ultra-large von Willebrand factor (ULvWF) mediated platelet adhesion characteristic of aTTP.2,9

Cablivi plus PEX+IMS provides protection from microthrombi within 24 hours.2,9

    ADAMTS13, a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13; aTTP, acquired thrombotic thrombocytopenic purpura; BSH, British Society for Haematology; ICU, intensive care unit; IMS, immunosuppression; IV, intravenous; NICE, National Institute for Health and Care Excellence; PEX, plasma exchange; SC, subcutaneous; ULvWF, ultra-large von Willebrand factor; vWF, von Willebrand factor.

    1. National Institute for Health and Care Excellence (NICE). Caplacizumab with plasma exchange and immunosuppression for treating acute acquired thrombotic thrombocytopenic purpura. TA667. December 2020. Available at: https://www.nice.org.uk/guidance/ta667 Accessed March 2022.
    2. CABLIVI Summary of Product Characteristics.
    3. Scully M, Cataland SR, Peyvandi F, et al. N Engl J Med. 2019;380(4):335–346.
    4. Coppo P, Bubenheim M, Axoulay E, et al. Blood. 2021;137(6);733–742.
    5. Peyvandi F, Scully M, Kremer Hovinga JA, et al. N Engl J Med. 2016;374(4):335–346.
    6. Peyvandi F, Cataland S, Scully M, et al. Blood Adv. 2021;5(8):2137–2141.
    7. Scully M, Hunt BJ, Benjamin S, et al. Br J Haematol. 2012;158(3):323–335.
    8. Scully M, Yarranton H, Liesner R, et al. Br J Haematol. 2008;142(5):819–826.
    9. Peyvandi F, Scully M, Kremer Hovinga J, et al. N Engl J Med. 2016;374(6):511–522.

MAT-GB-2105168 (v1.0)
Date of preparation: April 2022