Caplacizumab Produces Faster, Sustained Platelet Count Responses Than Placebo in aTTP

Patients with acquired thrombotic thrombocytopenic purpura (aTTP) who were treated with caplacizumab – anti–von Willebrand factor humanized immunoglobulin – experienced a faster and more sustained platelet count response compared with patients treated with placebo, according to results of the phase III HERCULES trial. The study authors, led by Paul Coppo, MD, of the Saint-Antoine University Hospital in Paris, also found that caplacizumab was associated with an earlier and more sustained benefit in terms of recurrence-free survival.

In a post hoc analysis of the HERCULES trial, Dr. Coppo and coauthors reviewed data from the intent-to-treat population, which included 72 patients with aTTP randomized to once-daily caplacizumab 10 mg and 73 patients with aTTP randomized to once-daily placebo. On the first day of treatment, either caplacizumab or placebo was administered via an intravenous injection prior to plasma exchange, followed by a subcutaneous injection in the abdominal region. Subcutaneous injections were used on subsequent days of treatment.

A higher proportion of patients in the caplacizumab arm had a rapid treatment response (defined as achieving a platelet count >150×109/L within 3 days), but the authors noted that normalization was achieved within 3 days in more than one-half of patients in both groups (78% vs. 59%, respectively). The initial rapid platelet count response was sustained with active therapy, as evidenced by an exacerbation rate of 3.6% in caplacizumab-treated patients in early responders, compared with 44.2% among early responders in the placebo group.

Rates of aTTP exacerbation (defined as having a recurrent aTTP episode within 30 days of therapeutic plasma exchange cessation) also were lower in patients who achieved a platelet count response after 3 days of treatment: 6.7% for caplacizumab-treated patients versus 30.0% for those who received placebo. While the exacerbation rate remained high among placebo-treated patients with an initial platelet response of >3 days, the rate was numerically lower when compared with faster responders, the authors added (TABLE).

Caplacizumab treatment reduced the median time to a durable response by more than half (4.5 vs. 10.5 days) and also was associated with a shorter median time to complete remission (40.0 vs. 44.2 days). In addition, treatment with caplacizumab appeared to lead to an earlier and sustained benefit, with a longer recurrence-free survival.

Despite this post-hoc analysis being limited by a lack of formal statistical testing, its findings “demonstrate that early benefit with caplacizumab is maintained and translates into clinically relevant improvements, as shown by reduced time to complete remission and extended recurrence-free survival,” the authors concluded.

Study authors report relationships with Ablynx, which sponsored the trial.


Coppo P, Scully M, de la Rubia J, et al. Caplacizumab induces fast and durable platelet count responses with improved time to complete remission and recurrence-free survival in patients with acquired thrombotic thrombocytopenic purpura. Abstract EP1626. Presented as part of EHA25 Virtual, June 14, 2020.