The key drivers of chronic morbidity risk in thalassemia1-4

Ineffective erythropoiesis and hemolysis are key drivers of thalassemia pathophysiology and can lead to serious complications1-4

  • In thalassemia, imbalanced α- and β-globin chain production increases oxidative stress and ATP (energy) demand in RBCs5
  • This triggers pathophysiological events leading to ineffective erythropoiesis (impaired production of healthy, mature RBCs) and hemolysis (premature breakdown of RBCs), which result in chronic anemia and downstream complications2,3
Flow chart showing different drivers of thalassemia and how they can cause potentially life-threatening complications

ATP=adenosine triphosphate; RBC=red blood cell.

NTDT and TDT patients have a significant disease burden that can lead to serious complications6,7

In patients with NTDT, chronic anemia is associated with increased risks of morbidity3,8-10

Complications can lead to end-organ damage6*

Charts illustrating complications in non–transfusion-dependent thalassemia patientsCharts illustrating complications in non–transfusion-dependent thalassemia patients
In a separate study,

49% of adults with NTDT who were referred to a thalassemia center of excellence in the United States ultimately required regular transfusions, reflecting substantial disease burden and late-stage complications.11†

NTD=non–transfusion dependent; NTDT=non–transfusion-dependent thalassemia.

*Study design: Large retrospective review of the medical charts of all (N=584) thalassemia intermedia patients currently registered at 6 comprehensive care centers in Lebanon, Italy, Iran, Egypt, United Arab Emirates, and Oman. Mean age was 25.44±13.86 years. Mean serum ferritin levels were 967.5 μg/L ± 853.9 μg/L. Treatment regimens included 23.8% (n=139) who received no transfusions, 24.5% (n=143) occasional transfusions, and 51.7% (n=302) regular transfusions; 34.6% (n=202) received hydroxyurea and 57.5% (n=336) iron chelation. The chart on the left shows data for the patients who received occasional transfusions (n=143). Occasional transfusions were defined as incidental transfusions for transient severe anemia secondary to infections, surgery, or pregnancy.6

†Study design: Multicenter cross-sectional chart review of 82 adults with NTDT referred to 1 of 3 US thalassemia specialty centers between 2013 and 2023. Patient charts were manually reviewed for clinical history, available genotype, laboratory features, and transfusion status after referral.11

Morbidity riskArrow

NTDT=non–transfusion-dependent thalassemia; TDT=transfusion-dependent thalassemia.

In patients with TDT, regular transfusions are associated with complications and logistical burden7,13

Greater transfusion burden is associated with more complications3,14,15

  • Risk of certain complications can increase with transfusion burden. In a claims-based study, patients receiving ≥12 RBC transfused units on average over a 12-week period experienced higher rates of complications compared with those who received none14
Heart icon
Cardiac complications14*
2.9×
Liver icon
Risk of liver disease14*
1.9×
Pancreas icon
Endocrine complications14*
3.2×
Transfusion dependent icon

Iron overload is an inherent risk of chronic transfusions, heightening the risk of serious complications and multi-organ damage16

RBC=red blood cell.

*Study design: Estimates are derived from a retrospective, claims-based study in Taiwan that included patients with a β-thalassemia claim from 1/1/01 to 12/31/16 (N=2984). Figures represent the ratio of the percentage of patient-years with cardiac, liver, and endocrine complications in patients receiving an average of ≥12 RBC transfusion units per 12-week period compared with patients receiving 0 RBC transfusion units.14

Logistical burdenArrow

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References: 1. Amid A et al, eds. Guidelines for the Management of ɑ-Thalassaemia. Thalassaemia International Federation; 2023. 2. Taher AT et al. Lancet. 2018;391(10116):155-167. doi:10.1016/S0140-6736(17)31822-6 3. Taher AT et al. N Engl J Med. 2021;384(8):727-743. doi:10.1056/NEJMra2021838 4. Taher AT et al, eds. Guidelines for the Management of Non-Transfusion-Dependent β-Thalassaemia. 3rd ed. Thalassaemia International Federation; 2023. 5. Kuo KHM. Hematology Am Soc Hematol Educ Program. 2023;2023(1):114-120. doi:10.1182/hematology.2023000468 6. Taher AT et al. Blood. 2010;115(10):1886-1892. doi:10.1182/blood-2009-09-243154 7. Taher AT et al, eds. Guidelines for the Management of Transfusion-Dependent β-Thalassaemia (TDT). 5th ed. Thalassaemia International Federation; 2025. 8. Musallam KM et al. Ann Hematol. 2022;101(1):203-204. doi:10.1007/s00277-020-04370-2 9. Musallam KM et al. Ann Hematol. 2021;100(7):1903-1905. doi:10.1007/s00277-021-04456-5 10. Blunt J et al. Br J Haematol. 2025;207(5):2204-2209. doi:10.1111/bjh.70123 11. Cheng A et al. Blood. 2025;146(suppl 1):1141-1142. doi:10.1182/blood-2025-1141 12. Musallam KM et al. Br J Haematol. 2025;207(4):1578-1588. doi.org/10.1111/bjh.70047 13. Paramore C et al. Patient. 2021;14(2):197-208. doi:10.1007/s40271-020-00473-0 14. Tang CH et al. Transfusion. 2021;61(10):2906-2917. doi:10.1111/trf.16636 15. Cappellini MD et al, eds. 2021 Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 4th ed. Thalassaemia International Federation; 2021. 16. Jobanputra M et al. Br J Haematol. 2020;191(5):897-905. doi:10.1111/bjh.17091 17. Ryan K et al. Value Health. 2019;22(suppl 3):S868-S869. doi:10.1016/j.jval.2019.09.2475

IMPORTANT SAFETY INFORMATION

BOXED WARNING: HEPATOCELLULAR INJURY

AQVESME can cause serious hepatocellular injury. Measure liver laboratory tests (ALT, AST, alkaline phosphatase and total bilirubin with fractionation) at baseline and every 4 weeks for 24 weeks and then as clinically indicated. Avoid use of AQVESME in patients with cirrhosis. Discontinue AQVESME if hepatic injury is suspected.
Because of the risk of hepatocellular injury, AQVESME is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the AQVESME REMS.

WARNINGS AND PRECAUTIONS

Hepatocellular Injury

AQVESME can cause hepatocellular injury. Avoid use of AQVESME in patients with cirrhosis. In patients with thalassemia treated with AQVESME, liver injury with and without jaundice has been observed within the first 6 months of exposure. Obtain liver tests (including ALT, AST, alkaline phosphatase, total bilirubin with fractionation) prior to the initiation of AQVESME, then every 4 weeks for the first 24 weeks, and as clinically indicated thereafter. Interrupt AQVESME if clinically significant increases in liver tests are observed or alanine aminotransferase is >5 times the upper limit of normal (ULN). Complete a comprehensive evaluation to rule out other causes of liver injury when drug-induced liver injury is suspected. Discontinue AQVESME if hepatocellular injury due to AQVESME is suspected.

Symptoms and signs of early liver injury may mimic those of thalassemia. Advise patients to report new or worsening symptoms of loss of appetite, nausea, right-upper-quadrant abdominal pain, vomiting, scleral icterus, jaundice, or dark urine while on AQVESME treatment.

During the double-blind period, 2 of 301 patients (0.66%) with thalassemia treated with AQVESME experienced adverse reactions suggestive of hepatocellular injury. Three additional patients experienced adverse reactions suggestive of hepatocellular injury during the open-label extension periods after switching from placebo to AQVESME. Of these 5 patients, 2 had serious liver injury requiring hospitalization, including 1 patient who developed jaundice (peak bilirubin 32 mg/dL). Another patient developed jaundice (peak bilirubin 4 mg/dL) without requiring hospitalization. These reactions were characterized by a time to onset within the first 6 months of treatment with peak elevations of alanine aminotransferase of >5×ULN with or without jaundice. All patients discontinued treatment with AQVESME, and these reactions improved upon treatment discontinuation.

AQVESME REMS

AQVESME is available only through a restricted program under a REMS called the AQVESME REMS because of the risk of hepatocellular injury.

ADVERSE REACTIONS

The most common adverse reactions among patients taking AQVESME were headache and insomnia.

DRUG INTERACTIONS

  • Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
  • Moderate CYP3A Inhibitors: Avoid concomitant use.
  • Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, see full Prescribing Information for recommended dosage for drug interactions with moderate CYP3A inducers.
  • Sensitive CYP3A Substrates, including hormonal contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
  • CYP2B6, CYP2C, and UGT1A1 Substrates: Monitor patients for efficacy of the substrates with narrow therapeutic index.
  • P-gp Substrates: Monitor patients for adverse reactions of the substrates with narrow therapeutic index.

HEPATIC IMPAIRMENT

Avoid use of AQVESME in patients with cirrhosis (Child-Pugh Class A, B, or C).

INDICATION

AQVESME is indicated for the treatment of anemia in adults with alpha- or beta-thalassemia.

Please see full Prescribing Information for AQVESME, including Boxed Warning.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: HEPATOCELLULAR INJURY

AQVESME can cause serious hepatocellular injury. Measure liver laboratory tests (ALT, AST, alkaline phosphatase and total bilirubin with fractionation) at baseline and every 4 weeks for 24 weeks and then as clinically indicated. Avoid use of AQVESME in patients with cirrhosis. Discontinue AQVESME if hepatic injury is suspected.
Because of the risk of hepatocellular injury, AQVESME is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the AQVESME REMS.

WARNINGS AND PRECAUTIONS

Hepatocellular Injury

AQVESME can cause hepatocellular injury. Avoid use of AQVESME in patients with cirrhosis. In patients with thalassemia treated with AQVESME, liver injury with and without jaundice has been observed within the first 6 months of exposure. Obtain liver tests (including ALT, AST, alkaline phosphatase, total bilirubin with fractionation) prior to the initiation of AQVESME, then every 4 weeks for the first 24 weeks, and as clinically indicated thereafter. Interrupt AQVESME if clinically significant increases in liver tests are observed or alanine aminotransferase is >5 times the upper limit of normal (ULN). Complete a comprehensive evaluation to rule out other causes of liver injury when drug-induced liver injury is suspected. Discontinue AQVESME if hepatocellular injury due to AQVESME is suspected.

Symptoms and signs of early liver injury may mimic those of thalassemia. Advise patients to report new or worsening symptoms of loss of appetite, nausea, right-upper-quadrant abdominal pain, vomiting, scleral icterus, jaundice, or dark urine while on AQVESME treatment.

During the double-blind period, 2 of 301 patients (0.66%) with thalassemia treated with AQVESME experienced adverse reactions suggestive of hepatocellular injury. Three additional patients experienced adverse reactions suggestive of hepatocellular injury during the open-label extension periods after switching from placebo to AQVESME. Of these 5 patients, 2 had serious liver injury requiring hospitalization, including 1 patient who developed jaundice (peak bilirubin 32 mg/dL). Another patient developed jaundice (peak bilirubin 4 mg/dL) without requiring hospitalization. These reactions were characterized by a time to onset within the first 6 months of treatment with peak elevations of alanine aminotransferase of >5×ULN with or without jaundice. All patients discontinued treatment with AQVESME, and these reactions improved upon treatment discontinuation.

AQVESME REMS

AQVESME is available only through a restricted program under a REMS called the AQVESME REMS because of the risk of hepatocellular injury.

ADVERSE REACTIONS

The most common adverse reactions among patients taking AQVESME were headache and insomnia.

DRUG INTERACTIONS

  • Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
  • Moderate CYP3A Inhibitors: Avoid concomitant use.
  • Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, see full Prescribing Information for recommended dosage for drug interactions with moderate CYP3A inducers.
  • Sensitive CYP3A Substrates, including hormonal contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
  • CYP2B6, CYP2C, and UGT1A1 Substrates: Monitor patients for efficacy of the substrates with narrow therapeutic index.
  • P-gp Substrates: Monitor patients for adverse reactions of the substrates with narrow therapeutic index.

HEPATIC IMPAIRMENT

Avoid use of AQVESME in patients with cirrhosis (Child-Pugh Class A, B, or C).

INDICATION

AQVESME is indicated for the treatment of anemia in adults with alpha- or beta-thalassemia.

Please see full Prescribing Information for AQVESME, including Boxed Warning.