--- title: "Takeda updates ADZYNMA labeling in U.S.; Boxed Warning: risk of neutralizing antibodies." sdDatePublished: "2026-08-24T16:18:00Z" source: "https://www.takeda.com/newsroom/statements/2026/update-on-adzynma/" topics: - name: "pharmaceutical" identifier: "medtop:20000223" - name: "medical research" identifier: "medtop:20000737" - name: "public health" identifier: "medtop:20001358" - name: "health care provider" identifier: "medtop:20000278" locations: - "Japan" - "United States" --- Takeda updates ADZYNMA labeling in U.S.; Boxed Warning: risk of neutralizing antibodies. Takeda Provides Update on ADZYNMA (ADAMTS13, recombinant-krhn) Takeda Provides Update on ADZYNMA (ADAMTS13, recombinant-krhn) Updated as of August 24, 2026 (originally published November 21, 2025) The health and safety of the patients we serve is our top priority. As such, in alignment with the U.S. Food and Drug Administration (FDA), we have updated the U.S. Prescribing Information for ADZYNMA® (ADAMTS13, recombinant-krhn) to include a Boxed Warning on the potential risk of developing neutralizing antibodies to ADAMTS13, as follows: “Neutralizing antibodies to ADAMTS13 with serious outcomes, including death, have been reported in patients treated with ADZYNMA. Neutralizing antibodies may result in decreased or lack of response to recombinant or plasma-derived ADAMTS13. Health care providers should monitor all patients closely for ADAMTS13 activity and development of ADAMTS13 neutralizing antibodies." Approved in November 2023, ADZYNMA is the only FDA-approved recombinant ADAMTS13 enzyme replacement therapy for adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP) designed to address the root cause of the disease. Neutralizing antibodies were not reported during the pivotal clinical trials in cTTP patients, however, occurrence of these antibodies has been reported with post-approval use of ADZYNMA. Neutralizing antibodies are a known potential risk when utilizing enzyme replacement therapies, and the original U.S. Prescribing Information contained a Warning and Precaution on the potential risk of neutralizing antibody development following treatment with ADZYNMA. The overall benefit risk profile of ADZYNMA remains favorable. cTTP is an ultra-rare, chronic blood clotting disorder associated with acute events and debilitating chronic symptoms or thrombotic thrombocytopenic purpura (TTP) manifestations. 1,2 When left untreated, acute TTP events have a mortality rate of more than 90 percent. 3 Patients with questions or concerns related to ADZYNMA should contact their health care provider. ADZYNMA (ADAMTS13, recombinant-krhn) is indicated for prophylactic or on-demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP). WARNING: NEUTRALIZING ANTIBODIES TO ADAMTS13 Neutralizing antibodies to ADAMTS13 with serious outcomes, including death, have been reported in patients treated with ADZYNMA. Neutralizing antibodies may result in decreased or lack of response to recombinant or plasma-derived ADAMTS13. Monitor all patients closely for ADAMTS13 activity and development of ADAMTS13 neutralizing antibodies. ADZYNMA is contraindicated in patients who have experienced life-threatening hypersensitivity reactions to ADZYNMA or its components. Hypersensitivity Reactions: Hypersensitivity reactions including anaphylaxis, may occur with ADZYNMA. Monitor patients for signs and symptoms of hypersensitivity reactions which may include tachycardia, chest tightness, wheezing and or acute respiratory distress, hypotension, generalized urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paresthesia, and restlessness. If signs and symptoms of severe hypersensitivity reactions occur, immediately discontinue administration of ADZYNMA and provide appropriate supportive care. Neutralizing Antibodies: Neutralizing antibodies to ADAMTS13 with serious outcomes including death have occurred following ADZYNMA administration. Neutralizing antibodies may result in a decreased or lack of response to ADZYNMA which could lead to serious disease related outcomes. Neutralizing antibodies were not reported in the cTTP clinical trials. All subjects had been previously exposed to ADAMTS13 through plasma-based products. There are no data on immunogenicity with ADZYNMA in previously untreated patients (subjects naïve to plasma-based products) Monitor all patients, including those who were previously exposed or naïve to plasma-based products, by assessing ADAMTS13 activity and ADAMTS13 neutralizing antibodies prior to initiation of ADZYNMA and periodically during the course of treatment. If expected ADAMTS13 activity levels are not attained or if acute TTP exacerbation occurs despite appropriate dose, perform an assay that measures ADAMTS13 neutralizing antibody concentrations. Laboratory tests for monitoring neutralizing antibody levels are not capable of distinguishing between inhibitors directed against ADZYNMA, the patient’s endogenous ADAMTS13, or ADAMTS13 from other plasma sources. Adverse Reactions: The most commonly observed adverse reactions (>5% of subjects) associated with ADZYNMA are headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness, and vomiting. Use in Specific Populations: The safety of ADZYNMA for use during pregnancy has not been established in controlled clinical trials. Limited data are insufficient to inform a drug associated risk of adverse developmental outcomes. There is no information regarding the presence of ADZYNMA in human milk, its effects on milk production, or the breastfed infant. To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov Please click for Full Prescribing Information Go to https: Alwan F, et al., Blood. 2019;133:1644-51. Kremer Hovinga JA, et al. Nat Rev Dis Primers. 2017;3:17020. Van Dorland H et al. Haematologica. 2019;104:2107-16. # Takeda Provides Update on ADZYNMA (ADAMTS13, recombinant-krhn) *Updated as of August 24, 2026 (originally published November 21, 2025)* The health and safety of the patients we serve is our top priority. As such, in alignment with the U.S. Food and Drug Administration (FDA), we have updated the U.S. Prescribing Information for ADZYNMA® (ADAMTS13, recombinant-krhn) to include a Boxed Warning on the potential risk of developing neutralizing antibodies to ADAMTS13, as follows: *“Neutralizing antibodies to ADAMTS13 with serious outcomes, including death, have been reported in patients treated with ADZYNMA. Neutralizing antibodies may result in decreased or lack of response to recombinant or plasma-derived ADAMTS13. Health care providers should monitor all patients closely for ADAMTS13 activity and development of ADAMTS13 neutralizing antibodies."* Approved in November 2023, ADZYNMA is the only FDA-approved recombinant ADAMTS13 enzyme replacement therapy for adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP) designed to address the root cause of the disease. Neutralizing antibodies were not reported during the pivotal clinical trials in cTTP patients, however, occurrence of these antibodies has been reported with post-approval use of ADZYNMA. Neutralizing antibodies are a known potential risk when utilizing enzyme replacement therapies, and the original U.S. Prescribing Information contained a Warning and Precaution on the potential risk of neutralizing antibody development following treatment with ADZYNMA. The overall benefit risk profile of ADZYNMA remains favorable. cTTP is an ultra-rare, chronic blood clotting disorder associated with acute events and debilitating chronic symptoms or thrombotic thrombocytopenic purpura (TTP) manifestations.1,2< sup> When left untreated, acute TTP events have a mortality rate of more than 90 percent.3< Patients with questions or concerns related to ADZYNMA should contact their health care provider. ## About ADZYNMA® (ADAMTS13, recombinant-krhn) ADZYNMA (ADAMTS13, recombinant-krhn) is indicated for prophylactic or on-demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).

WARNING: NEUTRALIZING ANTIBODIES TO ADAMTS13 <

  • Neutralizing antibodies to ADAMTS13 with serious outcomes, including death, have been reported in patients treated with ADZYNMA. Neutralizing antibodies may result in decreased or lack of response to recombinant or plasma-derived ADAMTS13. <
  • Monitor all patients closely for ADAMTS13 activity and development of ADAMTS13 neutralizing antibodies. < **ADZYNMA is contraindicated** in patients who have experienced life-threatening hypersensitivity reactions to ADZYNMA or its components. **Hypersensitivity Reactions:** Hypersensitivity reactions including anaphylaxis, may occur with ADZYNMA. Monitor patients for signs and symptoms of hypersensitivity reactions which may include tachycardia, chest tightness, wheezing and or acute respiratory distress, hypotension, generalized urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paresthesia, and restlessness. If signs and symptoms of severe hypersensitivity reactions occur, immediately discontinue administration of ADZYNMA and provide appropriate supportive care. **Neutralizing Antibodies:** Neutralizing antibodies to ADAMTS13 with serious outcomes including death have occurred following ADZYNMA administration. Neutralizing antibodies may result in a decreased or lack of response to ADZYNMA which could lead to serious disease related outcomes. Neutralizing antibodies were not reported in the cTTP clinical trials. All subjects had been previously exposed to ADAMTS13 through plasma-based products. There are no data on immunogenicity with ADZYNMA in previously untreated patients (subjects naïve to plasma-based products) Monitor all patients, including those who were previously exposed or naïve to plasma-based products, by assessing ADAMTS13 activity and ADAMTS13 neutralizing antibodies prior to initiation of ADZYNMA and periodically during the course of treatment. If expected ADAMTS13 activity levels are not attained or if acute TTP exacerbation occurs despite appropriate dose, perform an assay that measures ADAMTS13 neutralizing antibody concentrations. Laboratory tests for monitoring neutralizing antibody levels are not capable of distinguishing between inhibitors directed against ADZYNMA, the patient’s endogenous ADAMTS13, or ADAMTS13 from other plasma sources. **Adverse Reactions:** The most commonly observed adverse reactions (>5% of subjects) associated with ADZYNMA are headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness, and vomiting. **Use in Specific Populations:** The safety of ADZYNMA for use during pregnancy has not been established in controlled clinical trials. Limited data are insufficient to inform a drug associated risk of adverse developmental outcomes. There is no information regarding the presence of ADZYNMA in human milk, its effects on milk production, or the breastfed infant. **To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or [www.fda.gov ***Please click for [Full Prescribing Information](https: 1. Alwan F, et al., Blood. 2019;133:1644-51. 2. Kremer Hovinga JA, et al. Nat Rev Dis Primers. 2017;3:17020. 3. Van Dorland H et al. Haematologica. 2019;104:2107-16.