Nanobody can help treat acquired TTP
Image by Erhabor Osaro
TORONTO—Adding the anti-von Willebrand factor nanobody caplacizumab to standard therapy can provide clinical benefits for patients with
acquired thrombotic thrombocytopenic purpura (TTP), according to research presented at the 2015 ISTH Congress.
In the phase 2 TITAN trial, patients who received caplacizumab and standard therapy had a significantly shorter time to platelet normalization than patients who received standard therapy and placebo.
Caplacizumab was also associated with a shorter time to troponin, creatinine, and lactate dehydrogenase (LDH) normalization, as well as a reduced need for plasma exchange (PE).
However, some patients relapsed after stopping caplacizumab, and the majority of these relapses could be linked to unresolved disease activity. The drug also increased the risk of mild-to-moderate bleeding compared to placebo.
Flora Peyvandi, MD, PhD, of the University of Milan in Italy, presented data from the TITAN trial at ISTH as abstract LB006. Information on using ADAMTS13 activity for treatment monitoring in the TITAN trial was also presented at the meeting, as abstract OR363.
TITAN was sponsored by Ablynx, the company developing caplacizumab.
The study enrolled 75 patients with acquired TTP from January 2011 to January 2014. Patients were randomized to receive caplacizumab (n=36) or placebo (n=39).
All patients also received the current standard of care, which is, primarily, multiple PEs. The protocol for the study was adapted in September 2013 to allow 1 day of PE prior to study enrollment.
Patients in the caplacizumab arm immediately received an intravenous bolus dose of 10 mg and then a 10 mg subcutaneous dose of the drug daily until 30 days had elapsed after the final PE. Patients in the control arm received placebo at the same time points.
Platelet responses and relapse
The study’s primary endpoint was the time to platelet normalization. And patients in the caplacizumab arm achieved platelet normalization at more than twice the rate of patients in the placebo arm (overall hazard rate ratio=2.2, P=0.005).
Among patients with no prior PE, the median time to platelet normalization was 3 days in caplacizumab-treated patients (n=34) and 4.9 days in controls (n=35). Among patients with 1 prior PE, the median time to platelet normalization was 2.4 days in the caplacizumab arm (n=2) and 4.3 days in the placebo arm (n=4).
In the caplacizumab arm, a higher proportion of patients achieved a complete remission, and fewer patients had exacerbations of TTP. The complete remission rates were 81% and 46%, respectively. And the exacerbation rates were 8% and 28%, respectively.
However, the rate of exacerbation and/or relapse at up to 1 month of follow-up was the same in both arms, at 28%.
Seven patients relapsed within 10 days of stopping caplacizumab. All of these patients had continuous low ADAMTS13 activity (<10%) during and near the end of treatment.
Cardiac, renal, and tissue responses
Additional analyses revealed that patients in the caplacizumab arm had a faster time to troponin normalization than those in the placebo arm. At baseline, 53% of caplacizumab-treated patients and 46% of controls had elevated troponin. The median time to normalization was 9 days and 27 days, respectively.
Patients in the caplacizumab arm also had a faster time to creatinine normalization than those in the placebo arm. At baseline, 31% of caplacizumab-treated patients and 41% of controls had elevated creatinine. The median time to normalization was 4 days and 6 days, respectively.
And patients in the caplacizumab arm had a faster time to LDH normalization than those in the placebo arm. At baseline, 91% of caplacizumab-treated patients and 87% of controls had elevated LDH. The median time to normalization was 3 days and 4 days, respectively.
