AQVESME was studied in 2 clinical trials: ENERGIZE and ENERGIZE-T1

The ENERGIZE phase 3 trial evaluated the impact of AQVESME in NTDT1,2

ENERGIZE is a robust, multicenter, phase 3, randomized, double-blind, placebo-controlled study in adults with non–transfusion-dependent α- or β-thalassemia, followed by an open-label extension period1,2

ENERGIZE clinical trial randomization diagram of 194 patients with 2:1 ratio between AQVESME and placebo arms

Key inclusion criteria (N=194)

  • Adults with diagnosis of α- or β-thalassemia1†
  • Hb ≤10.0 g/dL1‡
  • ≤5 RBC units transfused during the 24-week period before randomization and no RBC transfusions ≤8 weeks before informed consent and during screening1

Primary endpoint

  • Hb response: ≥1.0 g/dL increase in average Hb from baseline (weeks 12–24)2

Other endpoint

  • Change in average FACIT-Fatigue score from baseline (weeks 12–24)2

FACIT-Fatigue=Functional Assessment of Chronic Illness Therapy–Fatigue Scale; Hb=hemoglobin; HbH=hemoglobin H; NTDT=non–transfusion-dependent thalassemia; RBC=red blood cell.

*Stratification by baseline Hb (≤9.0 g/dL vs 9.1-10.0 g/dL) and thalassemia genotype (α-thalassemia/HbH disease or β-thalassemia).1,2

†Based on Hb electrophoresis, Hb high-performance liquid chromatography, and/or DNA analysis.2

‡Based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the screening period.2

Baseline characteristics were generally well balanced1

Baseline disease characteristics§AQVESME (n=130)Placebo (n=64)
Hemoglobin (g/dL), n13064
Median (min, max)8.4 (5.3, 10.4)8.4 (5.9, 10.7)
Thalassemia genotype, n
α-thalassemia/HbH disease42 (32%)20 (31%)
β-thalassemia88 (68%)44 (69%)
Transfusion burden (RBC units),|| n
0114 (87.7%)54 (84.4%)
1–210 (7.7%)7 (10.9%)
3–56 (4.6%)3 (4.7%)
Reticulocyte (fraction of 1), n12258
Median (min, max)0.05 (0.00, 0.30)0.04 (0.00, 0.22)
Indirect bilirubin (mg/dL), n13062
Median (min, max)1.37 (0.13, 9.11)1.32 (0.15, 4.77)
LDH (U/L), n13064
Median (min, max)264 (108, 1208)267 (110, 1009)
Hepatic iron concentration (mg/g), n9852
Median (min, max)3.93 (0.75, 27.19)2.76 (0.75, 18.53)
History of splenectomy, n47 (36%)25 (39%)
History of cholecystectomy, n45 (35%)16 (25%)
History of iron chelation, n46 (35%)22 (34%)
History of hydroxyurea, n11 (8.5%)6 (9.4%)

LDH=lactate dehydrogenase.

§n is the number of patients with non-missing data.1

||Total number of RBC units transfused in the 24-week period before randomization.1

Explore the impact of AQVESME on Hb levels and fatigue in NTDT patients1

EXPLORE NTDT RESULTS

The ENERGIZE-T phase 3 trial evaluated the impact of AQVESME in TDT1,3,4

ENERGIZE-T is a robust, global, multicenter, phase 3, randomized, double-blind, placebo-controlled study in adults with transfusion-dependent α- or β-thalassemia

ENERGIZE-T clinical trial randomization diagram of 258 patients with 2:1 ratio between AQVESME and placebo arms

Key inclusion criteria (N=258)

  • Adults with diagnosis of α- or β-thalassemia1#
  • 6–20 RBC units transfused and a ≤6-week transfusion-free period in the 24 weeks prior to randomization1¶

Primary endpoint

  • Transfusion reduction response: ≥50% reduction in RBC transfusion burden with a reduction of at least 2 RBC units transfused in any consecutive 12-week period through week 48 compared with baseline1

HbE=hemoglobin E; TDT=transfusion-dependent thalassemia.

Eligible patients were stratified (AQVESME or placebo) by geographical region (North America and Europe; Asia-Pacific; and rest of world) and thalassemia genotype (subjects who do not have a β0 mutation at both alleles of the β-globin gene [non-β0/β0], including subjects with HbE/β-thalassemia or α-thalassemia/HbH disease; or subjects who have a β0 mutation at both alleles of the β-globin gene [β0/β0]).1,4

#Based on DNA analysis.4

Baseline characteristics were generally well balanced1

Baseline disease characteristicsAQVESME (n=171)Placebo (n=87)
Pretransfusion hemoglobin (g/dL)**
Median (min, max)9.0 (5.1, 11.8)8.9 (5.1, 10.9)
Thalassemia genotype, n
β0/β075 (44%)39 (45%)
non-β0/β0††96 (56%)48 (55%)
Transfusion burden (RBC units transfused in 24-week period before randomization), n
≤1254 (32%)21 (24%)
>12117 (68%)66 (76%)
Hepatic iron concentration (mg/g), n13374
Median (min, max)4.58 (0.37, 28.21)4.43 (0.37, 20.47)
History of splenectomy, n92 (54%)49 (56%)
History of cholecystectomy, n42 (25%)24 (28%)
History of iron chelation, n165 (96%)87 (100%)
History of hydroxyurea, n7 (4.1%)3 (3.4%)

**Pretransfusion Hb threshold is the mean of all pretransfusion Hb concentrations for the RBC transfusions administered during the 24-week period before randomization.1

††Non-β0/β0: Patients who do not have a β0 mutation at both alleles of the β-globin gene, including patients with HbE/β-thalassemia and α-thalassemia/HbH disease. β0/β0: Patients who have a β0 mutation at both alleles of the β-globin gene.1

Explore the impact of AQVESME on transfusion burden in TDT patients1

EXPLORE TDT RESULTS

References: 1. AQVESME. Prescribing Information. Agios Pharmaceuticals, Inc.; 2025. 2. Taher AT et al. Lancet. 2025;406(10498):33-42. doi:10.1016/S0140-6736(25)00635-X 3. Cappellini MD et al. Blood. 2024;144(suppl 1):409-411. doi:10.1182/blood-2024-200867 4. Data on file. Agios Pharmaceuticals, Inc.

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.