Written By: Pharmacally Medical News Desk
The U.S. Food and Drug Administration (FDA) on 21 November 2025 has launched an investigation into a reported death associated with Takeda’s Adzynma (recombinant ADAMTS13), a recently approved therapy for congenital thrombotic thrombocytopenic purpura (cTTP). The case involves a pediatric patient who developed neutralizing antibodies to ADAMTS13 after receiving Adzynma, ultimately leading to a fatal outcome. This marks the first reported death linked to the therapy since its approval in 2023 and has raised significant concerns about the immunogenicity risk of recombinant enzyme replacement in this rare disease population.
Case Details and FDA Investigation
The FDA issued a safety communication on November 21, 2025, confirming that a pediatric patient treated with Adzynma for cTTP died after developing neutralizing antibodies to ADAMTS13. According to the FDA, Prior to treatment with Adzynma, the reported pediatric patient with congenital thrombotic thrombocytopenic purpura (cTTP) had a history of severe allergic reactions to fresh frozen plasma (FFP), which is the conventional treatment to replace ADAMTS13 enzyme; After starting Adzynma, the patient developed neurologic symptoms. The patient had been receiving Adzynma prophylactically for nearly 10 months before neutralizing antibodies were detected. These antibodies are believed to have rendered the therapy ineffective, leading to a loss of ADAMTS13 enzyme activity and triggering a fatal thrombotic event. The agency stated that the death “appears to be related to Adzynma” and is now investigating the risk of neutralizing antibody formation and its potential for life-threatening or fatal outcomes in cTTP patients treated with the drug.
Adzynma is the first and only FDA-approved recombinant ADAMTS13 enzyme replacement therapy for cTTP, a rare genetic disorder characterized by severe deficiency of the ADAMTS13 enzyme. This enzyme is essential for cleaving ultra-large von Willebrand factor (VWF) multimers, preventing uncontrolled platelet aggregation and microthrombi formation. Without adequate ADAMTS13 activity, patients are at high risk for acute thrombotic events, organ damage, and death.
Mechanism of Neutralizing Antibodies
Neutralizing antibodies are immune proteins that bind to ADAMTS13 and block its enzymatic activity. In cTTP, the development of such antibodies can nullify the therapeutic effect of enzyme replacement, leading to a reappearance of disease activity. The FDA’s package insert for Adzynma notes that patients may develop neutralizing antibodies to ADAMTS13, which could result in a decreased or lack of response to therapy. The insert also states that neutralizing antibodies were not reported in clinical trials, but the risk in previously untreated patients (naïve to plasma-based therapies) is unknown. However, this case highlights that neutralizing antibodies can develop after prolonged exposure, especially in pediatric patients, and may have catastrophic consequences.
The FDA is working with Takeda to assess the risk of neutralizing antibody formation and to determine whether additional safety measures or labeling changes are needed. The agency has also encouraged healthcare providers to report any suspected adverse reactions related to Adzynma to the FDA’s MedWatch program.
References
FDA Investigating Death Due to Neutralizing Antibodies to ADAMTS13 following Adzynma Treatment of Congenital Thrombotic Thrombocytopenic Purpura, US FDA, 21 November 2025, https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-death-due-neutralizing-antibodies-adamts13-following-adzynma-treatment-congenital
Takeda Pharmaceuticals’ Genetic Disease Therapy under FDA Probe after Pediatric Patient Dies, 21 November 2025, Stocktwits, https://stocktwits.com/news-articles/markets/equity/takeda-pharmaceuticals-genetic-disease-therapy-under-fda-probe-after-pediatric-patient-dies/cLPMqISREO8
ADZYNMA (ADAMTS13, recombinant-krhn), Highlights of Prescribing Information, https://www.fda.gov/files/vaccines,%20blood%20&%20biologics/published/Package-Insert-and-Patient-Information-ADZYNMA.pdf
Scully M, et al, cTTP Phase 3 Study Investigators Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura, N Engl J Med. 2024 May 2;390(17):1584-1596. Doi: 10.1056/NEJMoa2314793. PMID: 38692292.