Caplacizumab Plus Standard Care Reduces Thromboembolic Events, Mortality in Patients with Thrombotic Thrombocytopenia Purpura

The standard of care for thrombotic thrombocytopenia purpura (TTP) is plasma exchange and immunosuppression, though many patients remain at risk for thrombotic complications until remission is achieved. Caplacizumab, an investigational anti-von Willebrand factor nanobody for the treatment of acquired TTP, was previously shown to shorten the time to resolution of TTP episodes, compared with placebo, in the phase II, randomized TITAN trial.

Flora Peyvandi, MD, PhD, associate professor of internal medicine at the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center in Milan, Italy, and TITAN investigators presented post-hoc data at the European Hematology Association’s 21st Congress, reporting that caplacizumab lowered the incidence of major thromboembolic events and mortality.

In TITAN, a total of 75 patients were randomized 1:1 to receive:

  • caplacizumab plus standard care (plasma exchange; n=36)
  • placebo plus standard of care (n=39)

Thirty-five caplacizumab-treated patients and 37 placebo-treated patients were included in the safety analysis.

Four major thrombotic events were reported in four patients in the caplacizumab group (TABLE), including one pulmonary embolism (PE) and three TTP exacerbations (defined as recurrences of TTP during the treatment period). The number of thrombotic events in the placebo group was higher, with 20 thrombotic events occurring in 14 patents, including 13 TTP exacerbations. The p value was not reported.

“Compared [with patients] who received placebo and standard care, a lower proportion of those treated with caplacizumab and standard care had one or more major thromboembolic adverse events (AEs) or died,” the authors noted.

Overall, 11.4 percent of patients treated with caplacizumab and 43.2 percent of patients treated with placebo experienced ≥1 thromboembolic events or died (p=0.006). Two deaths related to TTP occurred in the placebo group (one related to refractory TTP and one to cerebral hemorrhage), while no patients died in the caplacizumab cohort.

“The results suggest that treatment with caplacizumab has the potential to reduce the significant morbidity and mortality associated with acquired TTP,” the authors concluded.

The results are limited by the post-hoc analysis and need to be confirmed in other prospective studies. Dr. Peyvandi and colleagues noted that a phase III confirmatory study is ongoing and will include a prospectively defined assessment of TTP-associated morbidity and mortality.


Peyvandi F, Scully M, Kremer Hovinga JA, et al. Impact of caplacizumab treatment on mortality and major thromboembolic events in acquired TTP: Phase II TITAN study results. Abstract LB418. Presented at the EHA 21st Congress, June 10, 2016; Copenhagen, Denmark.

TABLE. Treatment-Emergent Adverse Events
Caplacizumab (n=35) Placebo (n=37)
Events Patients, n (%) Events Patients, n (%)
Acute myocardial infarction 0 0 2 2 (5.4%)
Deep-vein thrombosis 0 0 1 1 (2.7%)
Venous thrombosis 0 0 1 1 (2.7%)
Pulmonary embolism 1 1 (2.9%) 1 1 (2.7%)
Ischemic stroke 0 0 1 1 (2.7%)
Hemorrhagic stroke 0 0 1 1 (2.7%)
Thrombotic thrombocytopenic purpura exacerbations 3 3 (8.6%) 13 11 (29.7%)
Deaths related to TTP 0 0 2 2 (5.4%)
TOTAL 4 4 (11.4%) 22 16 (43.2%)