Caplacizumab

Summary

Caplacizumab (brand name Cablivi) is an anti-vWF nanobody approved for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in adults, in conjunction with plasma exchange and immunosuppression. It rapidly reduces microvascular thrombosis by blocking vWF-platelet interactions, leading to faster platelet count normalization and reduced aTTP-related morbidity and mortality.

Mechanism of Action

Caplacizumab is a bivalent nanobody that targets the A1 domain of von Willebrand factor (vWF), blocking the interaction between ultra-large vWF multimers and platelet glycoprotein Ib-alpha (GPIb-α), thereby inhibiting vWF-mediated platelet adhesion and aggregation and preventing microvascular thrombosis characteristic of acquired thrombotic thrombocytopenic purpura (aTTP).

Routes of Administration

Goals & Uses

• Prevention of aTTP exacerbation and recurrenceHematologyHigh
• Organ damage prevention (renal, neurological)End Organ ProtectionModerate
• Reduction of microvascular thrombosisAntithromboticHigh
• Treatment of acquired thrombotic thrombocytopenic purpura (aTTP)Hematology / Thrombotic DisorderHigh

Contraindications

• Active clinically significant bleedingHematologicHigh
• Hypersensitivity to caplacizumab or excipientsAllergy / ImmunologicHigh

Adverse Effects

• Hypersensitivity / anaphylaxisImmunologicalRare
• Injection site reactionsLocalCommon
• HeadacheNeurologicCommonPain in the head or upper neck
• Bleeding / hemorrhageHematologicCommon
• PyrexiaGeneralUncommon
• FatigueGeneralCommonLow energy or tiredness

Drug Interactions

• Antiplatelet agents (e.g., aspirin, clopidogrel)Moderate
• Anticoagulants (e.g., heparin, warfarin, DOACs)High
• Thrombolytics (e.g., alteplase)High

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patients (under 18 years)AgeRelative
• Severe hepatic impairmentOrgan ImpairmentRelative
• BreastfeedingReproductiveRelative

Regulatory Status

• European UnionApprovedApproved: Treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP), in conjunction with plasma exchange and immunosuppressionEMA approval granted September 3, 2018. First nanobody approved in the EU.
• United StatesApprovedApproved: Treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressive therapyFDA approval granted February 6, 2019. First nanobody approved by FDA.
• United KingdomApprovedApproved: Treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressive therapyApproved by MHRA following EU approval; NICE has issued guidance supporting use.

Approved by the EMA in September 2018 and by the FDA in February 2019 for adult patients with aTTP. It is the first approved nanobody-based therapeutic.

Evidence & Sources

No sources recorded yet.