Caplacizumab - Drug Monograph

Introduction

Caplacizumab (trade name Cablivi®) is a novel humanized bivalent nanobody that targets von Willebrand factor (vWF). It represents a significant advancement in the treatment of thrombotic thrombocytopenic purpura (TTP), a rare but life-threatening thrombotic microangiopathy. Approved by the FDA in 2019 and EMA in 2018, caplacizumab is the first specifically targeted therapy for acquired TTP, addressing the underlying pathophysiology of this condition.

Mechanism of Action

Caplacizumab binds to the A1 domain of von Willebrand factor with high affinity, inhibiting the interaction between vWF and platelets. This prevents the formation of microthrombi in small blood vessels, which is the hallmark pathological process in TTP. By blocking vWF-mediated platelet adhesion and aggregation, caplacizumab reduces the thrombotic complications while allowing plasma exchange and immunosuppressive therapy to address the autoimmune component (deficiency of ADAMTS13 protease).

Indications

• Treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressive therapy
• Used during the acute episode and continued for 30 days after the last plasma exchange

Dosage and Administration

• Initial dose: 11 mg intravenous bolus administered prior to initiation of plasma exchange
• Maintenance: 11 mg subcutaneous injection daily after plasma exchange
• Continue treatment for 30 days after the last plasma exchange session

• Renal impairment: No dosage adjustment required
• Hepatic impairment: Use with caution in severe hepatic impairment
• Elderly: No dosage adjustment required
• Pregnancy: Use only if potential benefit justifies potential risk
• Lactation: Decision should be made to discontinue nursing or discontinue drug

Pharmacokinetics

Contraindications

• Hypersensitivity to caplacizumab or any component of the formulation
• Active clinically significant bleeding
• History of severe hypersensitivity reactions to caplacizumab

Warnings and Precautions

• Serious and fatal bleeding events have been reported
• Monitor for signs and symptoms of bleeding
• Discontinue if severe bleeding occurs

• Use with caution in patients with increased bleeding risk
• Monitor patients undergoing concomitant anticoagulant or antiplatelet therapy
• Consider discontinuing 7 days prior to elective surgery
• Reversal agents: No specific antidote available

Drug Interactions

• Anticoagulants (warfarin, heparin, direct oral anticoagulants): Increased bleeding risk
• Antiplatelet agents (aspirin, clopidogrel, prasugrel): Increased bleeding risk
• Thrombolytics: Increased bleeding risk
• NSAIDs: Increased bleeding risk

Adverse Effects

• Epistaxis (nosebleeds)
• Headache
• Bleeding gums

• Vaginal bleeding
• Bruising
• Gastrointestinal bleeding
• Injection site reactions
• Fatigue
• Fever

• Intracranial hemorrhage
• Gastrointestinal hemorrhage
• Other severe bleeding events
• Hypersensitivity reactions

Monitoring Parameters

• Complete blood count with platelets
• Coagulation parameters (PT/INR, aPTT)
• ADAMTS13 activity and inhibitor levels
• Clinical assessment for bleeding risk

• Daily platelet counts during acute phase
• Signs and symptoms of bleeding
• Hemoglobin monitoring
• Injection site reactions
• Thrombocytopenia recurrence

• Monitor for TTP relapse for at least 30 days after discontinuation

Patient Education

• Caplacizumab increases the risk of bleeding
• Report any signs of bleeding immediately (unusual bruising, blood in urine/stool, prolonged bleeding from cuts)
• Use soft toothbrush and electric razor to minimize bleeding risk
• Avoid activities that may cause injury or bleeding
• Inform all healthcare providers about caplacizumab use, especially before any surgical procedures
• Proper subcutaneous injection technique if self-administering
• Importance of completing the full treatment course
• Recognize symptoms of TTP recurrence (neurological changes, fever, purpura)

• Refrigerate at 2-8°C
• Protect from light
• Do not freeze
• May be kept at room temperature (up to 25°C) for up to 2 months

References

1. Scully M, Cataland SR, Peyvandi F, et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346. 2. FDA prescribing information: Cablivi® (caplacizumab-yhdp) 3. Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016;374(6):511-522. 4. EMA assessment report: Cablivi® 5. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. 6. Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496-2502.