Indications for: CABLIVI
Treatment of acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.
The efficacy of Cablivi for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressive therapy was established in a pivotal multicenter, randomized, double-blind, placebo-controlled trial (HERCULES) (NCT02553317).
A total of 145 patients were enrolled in the HERCULES study. Patients were randomized to either Cablivi (n=72) or placebo (n=73). Patients in both groups received plasma exchange and immunosuppressive therapy. Patients were stratified according to the severity of neurological involvement (Glasgow Coma Scale score ≤12 or 13 to 15).
Patients received a single 11 mg Cablivi bolus intravenous injection or placebo prior to the first plasma exchange on study, followed by a daily subcutaneous injection of 11 mg Cablivi or placebo after completion of plasma exchange, for the duration of the daily plasma exchange period and for 30 days thereafter. If after the initial treatment course, sign(s) of persistent underlying disease such as suppressed ADAMTS13 activity levels remained present, treatment was extended for 7 day intervals for a maximum of 28 days.
The median treatment duration with Cablivi was 35 days.
The efficacy of Cablivi in patients with aTTP was established based on time to platelet count response (platelet count ≥150,000/µL followed by cessation of daily plasma exchange within 5 days). Time to platelet count response was shorter among patients treated with Cablivi, compared to placebo (Stratified log-rank test: P =0.01; Hazard Ratio: 1.55 [1.10; 2.20]).
Treatment with Cablivi resulted in a lower number of patients with aTTP-related death, recurrence of aTTP, or at least one treatment-emergent major thromboembolic event (a composite endpoint) during the treatment period vs plasma exchange and immunosuppression alone (12.7% vs 49.3%; P <.0001), as well as a significantly lower percentage of aTTP recurrences in the overall study period (13% vs 38%; P <.001).
Administer upon initiation of plasma exchange therapy. 1st bolus IV inj requires administration by healthcare provider. Give subsequent SC inj (after proper training) into the abdomen; rotate inj sites. Avoid inj around the navel. Day 1: Initially 11mg bolus IV inj at least 15mins prior to plasma exchange, then 11mg SC inj after plasma exchange completion. Subsequent Days (during daily plasma exchange): 11mg SC inj once daily following plasma exchange; (after plasma exchange period): 11mg SC inj once daily continuing for 30 days following the last daily plasma exchange; may further extend treatment for max 28 days if signs of persistent underlying disease are present (eg, suppressed ADAMTS13 activity levels). Discontinue if >2 recurrences of aTTP during treatment.
Increased risk of bleeding; interrupt treatment if severe; monitor closely. Withhold treatment 7 days prior to elective surgery, dental procedures, or other invasive interventions. Severe hepatic impairment; monitor closely. Coagulopathy (eg, hemophilia, other coagulation factor deficiencies). Pregnancy, neonates: monitor closely. Nursing mothers.
von Willebrand factor (vWF)-directed antibody fragment.
Avoid concomitant anticoagulants or antiplatelet agents; may increase risk of bleeding; monitor closely if needed.
Epistaxis, headache, gingival bleeding, fatigue, urticaria, pyrexia, paresthesia, dyspnea.
The available nonclinical data suggest unbound caplacizumab-yhdp is cleared renally.
Generic Drug Availability:
Single-dose vial—1 (w. diluent, supplies)