Safety data support use of caplacizumab in thrombotic thrombocytopenic purpura

Caplacizumab is a safe, well-tolerated treatment for patients with acquired thrombotic thrombocytopenic purpura, according to findings from an integrated analysis presented at the ASH Annual Meeting and Exposition.

“During the clinical development of caplacizumab [Ablynx], safety and tolerability data have been accrued from phase 1, phase 2 and phase 3 studies in three discrete populations,” the researchers wrote. “The objective of this integrated analysis is to characterize the safety and tolerability of caplacizumab based on summaries of data.”

Paul Knöbl, MD, PhD, of the division of hematology and hemostasis at Vienna University Hospital, and colleagues collected safety and tolerability data for caplacizumab in three distinct populations that included 790 patients, including 220 patients with acquired thrombotic thrombocytopenic purpura (TTP), 410 patients undergoing percutaneous coronary intervention and 160 healthy patients, although the indication for percutaneous coronary intervention is not being pursued, according to the researchers. The current analysis focused primarily on safety data from phase 2 and phase 3 studies in patients with TTP, including the TITAN and HERCULES studies.

Knöbl and colleagues examined data on treatment-emergent adverse events and clinical lab assessments, including hematology, biochemistry and coagulation markers. Treatment-related adverse bleeding events were of particular interest, as “caplacizumab blocks the interaction of the Willebrand factor A1 domain with the GPIb-IX-V platelet receptor” and the primary anticipated safety risk is bleeding, according to the researchers. Data were analyzed during the double-blind/single-blind treatment periods and the overall study period, including the follow-up period, for patients in the TTP group.

Almost all patients in the pooled TTP population (n = 216; 98.2%) were treated with at least one dose of study drug, including 106 patients in the caplacizumab group and 110 patients in the placebo group. The median duration of exposure to study drug was 35 days for patients in the caplacizumab group and 32.5 days in the placebo group.

The rates of treatment-emergent adverse events were similar between the caplacizumab (96.2%) and placebo (95.5%) groups. The following events were reported more often (5% difference) in the caplacizumab group compared with the placebo group: epistaxis (29.2% vs. 5.5%), headache (20.8% vs. 13.6%) and gingival bleeding (16% vs. 2.7%). Most of those events were classified as mild, according to the study results. Events that occurred more often in the placebo group included TTP (35.5% vs. 5.7%), hypokalemia (20% vs. 12.3%) and hypertension (12.7% vs. 4.7%).

The researchers also determined relative risks for the most common treatment-related adverse events. Gingival bleeding and epistaxis were much more likely among patients treated with caplacizumab, while TTP recurrence and hypertension were much more likely among patients in the placebo group.

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Serious adverse events were more frequent in patients treated with placebo compared with caplacizumab (49.1% vs. 29.2%, respectively), although TTP was the most commonly reported serious adverse event in both the placebo and caplacizumab groups (34.5% and 5.7%, respectively). All other reports of serious adverse events occurred in less than 5% of patients.

Treatment-related adverse bleeding events occurred more often among patients in the caplacizumab group compared with the placebo group (60.4% vs. 42.7%, respectively). These events were primarily mucocutaneous in nature; most were self-limiting and the majority resolved.

Rates of study drug discontinuation because of treatment-related adverse events were comparable between the caplacizumab and placebo groups (6.6% and 10%, respectively). In addition, these events occurred most often on an individual basis, excluding TTP and myocardial infarction.

Significant hematology and chemistry parameters generally stabilized over time, according to lab test results. Clinical lab values of importance were comparable between treatment groups and “very few” abnormalities were classified as treatment-emergent adverse events, according to the study findings. In addition, the safety profile associated with caplacizumab in other patient populations was similar to the profile seen in patients with TTP; no novel safety signals were observed. Treatment-related adverse bleeding events were observed most frequently among healthy patients and patients undergoing percutaneous coronary intervention.

“This integrated analysis has shown that caplacizumab is well-tolerated and has a favorable safety profile,” the researchers wrote. - by Julia Ernst, MS

Reference:

Knöbl P, et al. Abstract 3739. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.

Disclosures: Knöbl reports consultant/advisory board roles with Ablynx. Please see the abstract for all other authors’ relevant financial disclosures.