Caplacizumab is safe and effective in patients with iTTP

Post-trial data support caplacizumab's long-term safety and efficacy in acquired or immune-mediated thrombotic thrombocytopenic purpura patients.

The drug's safety also applies to long-term treatments 

Acquired or immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare thrombotic microangiopathy that is characterised by thrombocytopenia and haemolytic anaemia. Recently, the HERCULES trial (NCT02553317) showed that among patients with iTTP, treatment with caplacizumab was associated with faster normalisation of the platelet count; with a lower incidence of a composite of iTTP-related death, recurrence of iTTP, or a thromboembolic event during the treatment period; and with a lower rate of recurrence of iTTP during the trial than placebo1. However, follow-up in the HERCULES trial was 28 days after the end of treatment. To evaluate the long-term safety and efficacy of caplacizumab in patients with iTTP, and safety and efficacy of repeated use of caplacizumab for iTTP recurrence, the post-HERCULES trial (NCT02878603) was performed. Prof. Marie Scully (University College London Hospitals, UK) presented the results2

Participants who completed the HERCULES trial were invited to attend twice-yearly visits, for 3 years. In case of iTTP exacerbation or relapse (recurrence) during post-HERCULES, patients could receive open-label caplacizumab with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST). Of 104 patients who enrolled in HERCULES, 75 had been treated with caplacizumab with TPE plus IST (Capla group) and 29 had been treated with TPE plus IST only (placebo group).

Repeated use for iTTP recurrence, and no increases in relapse

Of the patients in the Capla group, 11 (15%) patients had ≥1 recurrence during post-HERCULES; 8 of them were re-treated with caplacizumab. In the placebo group, 8 (28%) patients had ≥1 recurrence during post-HERCULES; 5 of them were treated with caplacizumab. All first and second recurrences treated with caplacizumab were resolved, whereas only 4 out of 6 patients with recurrence who were not treated with caplacizumab resolved during post-HERCULES; 1 patient died from iTTP disease after recurrence, this patient did not receive caplacizumab in HERCULES or post-HERCULES. 

The frequency of (serious) adverse events was generally similar between the Capla group and the placebo group during post-HERCULES, e.g. for headache (21% vs 31%), acute TTP (15% vs 28%), nasopharyngitis (8% vs 21%), and bleeding events (21% vs 31%). 

Prof. Scully summarised that “these data support the long-term safety and efficacy of caplacizumab, including its repeated use for iTTP recurrence. In addition, there were no observed increases in relapse or exacerbation of iTTP in patients receiving caplacizumab versus placebo.”

1. Scully M, et al. N Engl J Med 2019;380:335–346.
2. Scully M, et al. Long-term safety and efficacy of caplacizumab for acquired thrombotic thrombocytopenic purpurea (aTTP): the post-HERCULES study. Abstract S294. EHA2022 Hybrid Congress, 09–12 June.