Caplacizumab
Also known as: ALX-0681, ALX‑0681, anti-vWF nanobody, Cablivi, Caplacizumab‑yhdp
Source Caplacizumab at Peptiology
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Summary
Caplacizumab is a humanized, bivalent nanobody that targets von Willebrand factor (vWF) and is approved for the treatment of acquired immune thrombotic thrombocytopenic purpura (iTTP). Used together with plasma exchange and immunosuppression, it shortens the time to platelet count recovery and lowers the risk of early disease recurrence, though it raises the likelihood of mild bleeding.
Mechanism of Action
Caplacizumab binds the A1 domain of ultra‑large vWF multimers, blocking their interaction with platelet glycoprotein Ib‑IX‑V receptors. In iTTP, severe ADAMTS13 deficiency allows these multimers to accumulate and trigger microvascular platelet aggregation. By preventing platelet adhesion, the nanobody interrupts the cascade that leads to microthrombi, ischemic organ injury, and the characteristic thrombocytopenia and hemolysis.
What the Research Shows
Randomised, double‑blind trials (e.g., the HERCULES study, 145 patients) showed that caplacizumab, given as a 10 mg IV loading dose followed by daily 10 mg sub‑cutaneous injections, reduced the median time to platelet normalization (2.69 vs 2.88 days) and increased the likelihood of achieving normalization by 55 %. The composite endpoint of TTP‑related death, recurrence, or thrombo‑embolic event was 74 % lower (12 % vs 49 %) and overall recurrence during follow‑up fell by 67 % (12 % vs 38 %). Reviews note that caplacizumab, the first approved nanobody drug (2018), is now incorporated into front‑line regimens for iTTP alongside plasma exchange and steroids. Evidence is confined to acquired iTTP; data on congenital forms are lacking.
Reported Benefits
Clinical trials demonstrate faster platelet recovery, reduced need for plasma exchange, shorter hospitalisation, and a marked decline in early relapse and composite adverse outcomes. When added to standard plasma exchange and immunosuppression, caplacizumab improves 30‑day remission rates and appears to lower the incidence of life‑threatening thrombotic complications.
Limitations of the Evidence
Evidence is limited to acquired iTTP; the drug has not been formally studied in congenital TTP or other thrombotic disorders. Long‑term safety beyond the trial period remains incompletely characterised. The benefit on overall mortality is unclear, and the requirement for continued dosing until ADAMTS13 activity normalises adds complexity. Cost and access considerations are not addressed in the published data.
Safety Considerations
Caplacizumab increases the risk of bleeding, most commonly mild mucocutaneous hemorrhage (reported in 65 % of treated patients versus 48 % with placebo). A modest absolute increase in bleeding events (≈17 % risk difference) was noted, and clinicians should monitor for overt bleeding, especially in patients with pre‑existing bleeding tendencies. No major fatal bleeding was directly linked to the drug in the cited trials, but caution is advised.
How It Is Administered
Caplacizumab is administered intravenously as a single 10 mg loading dose, then sub‑cutaneously at 10 mg once daily. Treatment starts alongside therapeutic plasma exchange and continues for at least 30 days, or until ADAMTS13 activity recovers, whichever is longer. The drug is supplied as a nanobody formulation suitable for both routes.
Routes of Administration
Goals & Uses
- Accelerate platelet count normalizationTherapeuticHigh
- Prevention of aTTP exacerbation and recurrenceHematologyHigh
- Organ damage prevention (renal, neurological)End Organ ProtectionModerate
- Reduction of microvascular thrombosisAntithromboticHigh
- Prevent aTTP relapseTherapeuticHigh
- 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
- Injection site reactionLocalCommonRedness, swelling, itching, bruising, or pain at the injection site
- Bleeding (e.g., epistaxis, gingival bleeding)HematologicCommon
Drug Interactions
- Antiplatelet agents (e.g., aspirin, clopidogrel)Moderate
- Anticoagulants (e.g., heparin, warfarin, DOACs)High
- Thrombolytics (e.g., alteplase)High
- Anticoagulants (e.g., warfarin, heparin)Moderate
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric patients (under 18 years)AgeRelative
- Severe hepatic impairmentOrgan ImpairmentRelative
- BreastfeedingReproductiveRelative
- Pediatric patients <12 yearsAgeAbsolute
Regulatory Status
- European UnionApprovedApproved: Acquired thrombotic thrombocytopenic purpura (aTTP) in adults and adolescents ≥12 yearsEMA approval 2019.
- United StatesApprovedApproved: Acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressionFDA approval 2019; marketed as Cablivi.
- 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 FDA (US) and EMA (EU) for adult and adolescent (≥12 y) aTTP; marketed under the brand name Cablivi.
Evidence & Sources
- Journal ArticleModeratePishko AM, Li A, Cuker A2025-01-01T00:00:00.000000Z
- Journal ArticleModerateScully M, et al.2019-01-01T00:00:00.000000Z
- Journal ArticleModerateJin BK, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleModerateJovčevska I, Muyldermans S2020-01-01T00:00:00.000000Z
- Journal ArticleModerateJoly BS, Coppo P, Veyradier A2017-01-01T00:00:00.000000Z
- Journal ArticleModerateSukumar S, Lämmle B, Cataland SR2021-01-01T00:00:00.000000Z
Frequently Asked Questions
What condition is caplacizumab approved to treat?
It is approved for acquired immune thrombotic thrombocytopenic purpura (iTTP), used together with plasma exchange and immunosuppressive therapy.
How does caplacizumab work to stop TTP symptoms?
The nanobody binds von Willebrand factor multimers, preventing them from attaching to platelets and thereby blocking the formation of microvascular platelet clots that cause thrombocytopenia and organ injury.
What are the main benefits of adding caplacizumab to standard TTP therapy?
Clinical trials show it speeds platelet count recovery, reduces early disease recurrence, lowers the composite risk of death, relapse or thrombo‑embolic events, and shortens the duration of plasma exchange and hospital stay.
What safety concerns should patients be aware of?
The most common adverse effect is mild mucocutaneous bleeding; overall bleeding risk is higher than with standard care, so patients with bleeding disorders or on anticoagulants need careful monitoring.
How is caplacizumab given to patients?
A 10 mg intravenous loading dose is followed by daily 10 mg sub‑cutaneous injections, continued for at least 30 days or until laboratory recovery of ADAMTS13 activity.
What is Caplacizumab?
Caplacizumab is a humanized, bivalent nanobody that targets von Willebrand factor (vWF) and is approved for the treatment of acquired immune thrombotic thrombocytopenic purpura (iTTP). Used together with plasma exchange and immunosuppression, it shortens the time to platelet count recovery and lowers the risk of early disease recurrence, though it raises the likelihood of mild bleeding.
What is Caplacizumab used for?
Caplacizumab is educationally associated with: Accelerate platelet count normalization, Prevention of aTTP exacerbation and recurrence, Organ damage prevention (renal, neurological), Reduction of microvascular thrombosis, Prevent aTTP relapse, Treatment of acquired thrombotic thrombocytopenic purpura (aTTP). Educational only — not medical advice.
How is Caplacizumab administered?
Recorded routes of administration: Intravenous, Subcutaneous.
What are the potential side effects of Caplacizumab?
Reported adverse effects include: Hypersensitivity / anaphylaxis, Injection site reactions, Headache, Bleeding / hemorrhage, Pyrexia, Fatigue, Injection site reaction, Bleeding (e.g., epistaxis, gingival bleeding). This list is not exhaustive — consult a qualified clinician.
Who should avoid Caplacizumab?
Recorded contraindications: Active clinically significant bleeding, Hypersensitivity to caplacizumab or excipients. Consult a qualified clinician before use.