FDA approves caplacizumab for pediatric acquired thrombotic thrombocytopenic purpura

The FDA has approved Cablivi (caplacizumab-yhdp; Sanofi) for injection for the treatment of pediatric patients aged 12 years and older with acquired thrombotic thrombocytopenic purpura (aTTP), to be used in combination with plasma exchange and immunosuppressive therapy. The approval expands the indication for caplacizumab, which was initially approved in 2019 for the treatment of adults with aTTP.

Acquired thrombotic thrombocytopenic purpura is a rare, life-threatening thrombotic microangiopathy characterized by widespread platelet-rich microthrombi in small blood vessels. Although the condition is most often diagnosed in adults, pediatric cases do occur and are associated with substantial morbidity. The estimated annual incidence of aTTP in children is approximately 1 per 10 million, underscoring the rarity of the disease in this population.

In aTTP, immune-mediated deficiency of ADAMTS13 activity leads to accumulation of ultra-large von Willebrand factor multimers, resulting in platelet aggregation and microvascular thrombosis. These pathologic clots can impair blood flow to critical organs, including the brain, heart, and kidneys. Clinically, patients often present with thrombocytopenia, microangiopathic hemolytic anemia, and variable degrees of neurologic, renal, or cardiac involvement. Prompt recognition and treatment are essential to prevent organ damage and death.

Caplacizumab is a humanized, bivalent nanobody that targets the A1 domain of von Willebrand factor, inhibiting its interaction with platelets and thereby reducing microthrombus formation. In adults with aTTP, the addition of caplacizumab to standard therapy has been shown to shorten the time to platelet count normalization and reduce the incidence of disease exacerbations. Until now, evidence supporting its use in pediatric patients has been limited.

The pediatric approval was supported by efficacy data from a retrospective chart review study that included 30 patients with aTTP ranging in age from 2 to 18 years. In this analysis, 80% of patients achieved clinical remission. Remission was defined as normalization of platelet counts with lactate dehydrogenase levels less than 1.5 times the upper limit of normal for a duration of 30 days or longer. These findings suggest that caplacizumab may provide clinically meaningful benefit when incorporated into combination therapy for pediatric aTTP, consistent with outcomes observed in adult populations.

Safety considerations remain central to the use of caplacizumab in both pediatric and adult patients. Because the drug interferes with normal clot formation, treatment is associated with an increased risk of bleeding, including serious and potentially fatal hemorrhagic events. The risk is heightened in patients with underlying coagulopathies or those receiving concomitant antiplatelet agents or anticoagulants. Clinical guidance recommends discontinuation of therapy if clinically significant bleeding occurs.

Additional precautions include holding caplacizumab for at least 7 days prior to elective surgery, dental procedures, or other invasive interventions to reduce bleeding risk. The drug is contraindicated in patients with a known severe hypersensitivity reaction to caplacizumab or any of its components. In the pediatric population evaluated, the most commonly reported adverse events included epistaxis, headache, and gingival bleeding, consistent with the known safety profile of the medication.

Cablivi has received Orphan Drug Designation for the treatment of pediatric aTTP, reflecting both the rarity of the condition and the unmet medical need in this population. The designation is intended to encourage the development and availability of therapies for rare diseases by providing regulatory and development incentives.

For pediatric hematologists and other clinicians involved in the care of children and adolescents with aTTP, the expanded approval provides an additional therapeutic option that aligns pediatric management more closely with established adult treatment paradigms. Given the severity of aTTP and the challenges of managing this condition in younger patients, the availability of caplacizumab for adolescents aged 12 years and older represents a notable development in the treatment landscape.

Reference

FDA. FDA approves therapy for rare blood disorder in pediatric patients 12 years and older. FDA. January 5, 2026. Accessed January 5, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-therapy-rare-blood-disorder-pediatric-patients-12-years-and-older