By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved the first therapy for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP). Caplacizumab-yhdp is a von Willebrand factor (vWF)-directed antibody fragment produced by recombinant DNA in Escherichia coli bacteria. The drug is considered a “nanobody,” a novel class of therapeutic proteins that are fragments of antibodies. It is marketed as Cablivi.
Caplacizumab-yhdp is indicated for the treatment of aTTP in combination with plasma exchange and immunosuppressive therapy.1
The recommended dose is 11 mg as an IV bolus at least 15 minutes prior to plasma exchange and 11 mg subcutaneously (SQ) after completion of plasma exchange on day 1.1 Subsequent treatment is 11 mg SQ once daily following plasma exchange. This is followed by 11 mg SQ once daily for 30 days beyond the last plasma exchange. Depending on signs of persistent underlying disease (e.g., suppressed ADAMTS13 activity), treatment may be extended for a maximum of 28 days. If the patient experiences more than two recurrences of aTTP, caplacizumab-yhdp should be discontinued. Caplacizumab-yhdp is available as an 11 mg lyophilized powder in a single-dose vial.
Caplacizumab-yhdp plus plasma exchange is associated with faster normalization of platelet count and a lower incidence of aTTP-related death and recurrence.1,2
Bleeding-rated adverse events (mainly mucocutaneous) were more common in patients taking caplacizumab-yhdp compared to those on plasma exchange plus placebo (65% vs. 48%).1,2
The rate of serious adverse events of bleeding was 11% for caplacizumab-yhdp vs. 1% for placebo.
aTTP is caused by the development of autoantibodies that inhibit the activity of the vWF-cleaving protease ADAMTS13.3 The result is hemolytic anemia, thrombocytopenia, and tissue infarction. Caplacizumab-yhdp binds to vWF, inhibiting the binding between vWF and platelets and reducing vWF-mediated platelet adhesion and consumption.1
The efficacy of caplacizumab-yhdp was evaluated in a randomized, double-blind, placebo-controlled study that included 145 subjects with aTTP.1,2 Subjects were randomized to caplacizumab-yhdp or placebo in addition to standard care, which was defined as daily plasma exchange up to two days after normalization of platelet count (≥ 150,000 µL). Prednisone or prednisolone was administered during the plasma-exchange period and continued for the first week, after which it could be tapered and discontinued within 30 days after the last plasma exchange. Caplacizumab-yhdp was continued for 30 days after completion of plasma exchange and could be extended at seven-day intervals up to 28 days. The primary endpoint was the time to normalization of platelet count. Secondary endpoints were a composite of aTTP-related death, recurrence of aTTP, or a major thromboembolic event.
The median time to platelet response was statistically shorter with caplacizumab-yhdp (2.69 vs. 2.88 days; P = 0.01). There were nine events in the caplacizumab-yhdp group compared to 36 events for placebo (P < 0.0001). There were zero deaths, three patients with recurrence of aTTP, and six patients with major thromboembolic events in the caplacizumab-yhdp group. The corresponding events in the placebo group were three deaths, 28 patients with recurrence of aTTP, and six patients with major thromboembolic events. The caplacizumab-yhdp group demonstrated a lower volume of plasma exchange (median 18.1 L vs. 26.9 L in the placebo group), fewer days of hospitalization (median nine days vs. 12 days in the placebo group), and fewer days in the ICU (median three days vs. five days in the placebo group).2
aTTP is a rare and life-threatening disorder.4 Current treatment calls for plasma exchange to replenish functioning ADAMTS13 and remove vWF autoantibodies. Glucocorticoids are administered to suppress anti-ADAMTS13 autoantibodies.2 The addition of caplacizumab-yhdp accelerates platelet recovery, lowers adverse outcomes (composite of death and recurrence), and possibly reduces healthcare resource use.
The estimated average cost for treating a typical aTTP episode with caplacizumab-yhdp is $270,000.
- Genzyme Corporation. Cablivi Prescribing Information, February 2019. Available at: . Accessed Feb. 22, 2019.
- Scully M, Cataland SR, Peyvandi F, et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med 2019;380:335-346.
- Sadler JE. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood 2008;112:11-18.
- U.S. Food and Drug Administration. FDA approves first therapy for the treatment of adult patients with a rare blood clotting disorder, Feb. 6, 2019. Available at: . Accessed Feb. 22, 2019.