On February 6, 2019, in conjunction with plasma exchange and immunosuppressive treatment, the Food and Drug Administration approved caplacizumab-yhdp (CABLIVI, Ablynx NV) for adult patients with acquired thrombotic thrombocytopenic purpura (aTTP).
The approval was based on a multicenter randomized, double-blind, placebo-controlled trial (HERCULES) (NCT02553317) involving 145 caplacizumab-yhdp (n=72) or placebo (n=73) randomized patients. Plasma exchange and immunosuppressive therapy were given to patients in both classes. Patients obtained a single 11 mg intravenous injection of caplacizumab-yhdp bolus or placebo prior to the first plasma exchange study accompanied by a daily subcutaneous injection of caplacizumab-yhdp (11 mg) or placebo following completion of the plasma exchange, for a duration of daily plasma exchange, and for a period of 30 days afterwards.
If after the initial treatment course, signs 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.
Caplacizumab-yhdp efficacy was determined on the basis of time-to-platelet count response (platelet count ~150,000/μL followed by daily plasma exchange cessation within 5 days). Compared to placebo, the time-to-platelet count response was faster among patients treated with caplacizumab-yhdp. Caplacizumab-yhdp therapy resulted in a lower number of patients during the treatment period with TTP-related deaths (0 vs. 3) and TTP recurrence (3 vs. 28). The proportion of patients with recurrence of TTP was lower in the caplacizumab-yhdp group (9/72 patients [13%]) compared to those receiving placebo (28/73 patients [38%]; p<0.001) over the total study duration (drug treatment period plus 28-day follow-up following discontinuation of drug treatment).
Epistaxis, fever, and gingival bleeding were the most common adverse reactions in at least 15 percent of patients receiving caplacizumab-yhdp.
The prescribed first dose of caplacizumab-yhdp is 11 mg bolus intravenous injection at least 15 minutes prior to plasma exchange, followed by 11 mg subcutaneous injection at the end of plasma exchange, 30 days after the last plasma exchange, on a daily basis. View the full prescription information for CABLIVI for additional dosing information.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
