1. Home
  2. Vaccines, Blood & Biologics
  3. Safety & Availability (Biologics)
  4. FDA Investigating Death Due to Neutralizing Antibodies to ADAMTS13 following Adzynma Treatment of Congenital Thrombotic Thrombocytopenic Purpura
  1. Safety & Availability (Biologics)

FDA Investigating Death Due to Neutralizing Antibodies to ADAMTS13 following Adzynma Treatment of Congenital Thrombotic Thrombocytopenic Purpura

FDA Safety Communication – November 21, 2025

Summary of the Issue

Since approval, the Food and Drug Administration (FDA) has received postmarketing reports of neutralizing antibodies to ADAMTS13, including one death, in congenital thrombotic thrombocytopenic purpura patients treated with Adzynma (ADAMTS13, recombinant-krhn). Adzynma is a recombinant ADAMTS13 (rADAMTS13) indicated for prophylactic or on-demand enzyme replacement therapy in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).  Adzynma contains two versions of rADAMTS13: native sequence and variant sequence (rADAMTS13.R97) that differs from the native sequence by a single amino acid.

The reported death in a pediatric cTTP patient appears to be related to Adzynma. Prior to treatment with Adzynma, this patient had severe allergic reactions to fresh frozen plasma (FFP). The patient presented with neurologic symptoms which progressed, and the presence of neutralizing antibodies to ADAMTS13 was identified approximately 10 months after starting prophylactic treatment with Adzynma. It is important to note that current assays are unable to distinguish neutralizing antibodies to recombinant ADAMTS13 from neutralizing antibodies to endogenous ADAMTS13.

The U.S. prescribing information (USPI) includes information on the potential risk of development of neutralizing antibodies following treatment with Adzynma under Warnings and Precautions – Immunogenicity. The Patient Package Insert for this product instructs patients to consult with their healthcare provider for monitoring with blood tests for the development of inhibitors to ADAMTS13. Neutralizing antibodies were not reported in the cTTP clinical trials, and the current labeling does not include information regarding postmarketing reports of neutralizing antibodies associated with serious, including fatal, outcomes.

FDA is investigating the risk of development of neutralizing antibodies with serious, including life-threatening or fatal, outcomes following treatment with Adzynma and is evaluating the need for further regulatory action.

To report suspected adverse events including neutralizing antibodies, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Back to Top