Mitapivat

Mitapivat is a pyruvate kinase activator that acts by allosterically binding to the pyruvate kinase tetramer and increasing pyruvate kinase (PK) activity. Imbalances in globin chain production during erythropoiesis result in increased oxidative stress, which leads to ineffective erythropoiesis and hemolysis.

• AQVESME is indicated for the treatment of anemia in adults with alpha- or beta-thalassemia. AQVESME is a pyruvate kinase activator indicated for the treatment of anemia in adults with alpha- or beta-thalassemia.ICD-10: D64.9

• None. None.contraindicated

The tablet should be swallowed whole. Do not split, crush, chew, or dissolve the tablets. ( 2.1 ) Recommended dose is 100 mg orally twice daily with or without food. ( 2.2 ) 2.1 Important Dosage and Administration Information AQVESME is taken with or without food. Swallow tablets whole. Do not split, crush, chew, or dissolve the tablets. If a dose of AQVESME is missed by 4 hours or less, administer the dose as soon as possible. If a dose of AQVESME is missed by more than 4 hours, do not administer a replacement dose, and wait until the next scheduled dose. Subsequently, return to the normal dosing schedule. Monitor for hepatocellular injury during treatment with AQVESME [see Dosage and Administration (2.3) ] . 2.2 Recommended Dosage The recommended dosage for adults with alpha- or beta-thalassemia is AQVESME 100 mg orally twice daily. Treatment with AQVESME is intended to be long-term. Discontinue AQVESME if no benefit in hemolytic anemia has been observed, based on the totality of laboratory results and clinical status of the patient, unless there is another explanation for response failure (e.g., bleeding, surgery, other concomitant illnesses). Interruption or Discontinuation If a patient needs to interrupt or discontinue AQVESME for any reason, a dose taper is not necessary. 2.3 Monitoring for Safety Prior to Initiating Treatment with AQVESME Check liver tests including ALT, AST, alkaline phosphatase, total bilirubin with fractionation, before first AQVESME dose.

5.1 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 (DILI) is suspected. Discontinue AQVESME if hepatocellular injury due to AQVESME is suspected [see Dosage and Administration (2.3) ] . 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.

The following clinically significant adverse reaction is described elsewhere in labeling: Hepatocellular Injury [see Warnings and Precautions (5.1) ]. The most common adverse reactions were headache and insomnia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Agios Pharmaceuticals, Inc. at 1-833-228-8474 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Alpha- and Beta-Thalassemia A total of 301 patients with thalassemia received AQVESME, administered at 100 mg orally twice daily, for up to 59.9 weeks in the ENERGIZE trial (N=129) and the ENERGIZE-T trial (N=172) [see Clinical Studies (14) ] . ENERGIZE Trial Patients with non-transfusion-dependent thalassemia received AQVESME (N=129) or placebo (N=63). The most common adverse reactions (≥5% and at least 5% higher in the AQVESME arm) in patients with non-transfusion-dependent thalassemia were headache and insomnia. ENERGIZE-T Trial Patients with transfusion-dependent thalassemia received AQVESME (N=172) or placebo (N=85). The most common adverse reactions (≥5% and at least 5% higher in the AQVESME arm) in patients with transfusion-dependent thalassemia were headache and insomnia.

Hepatic Impairment: Avoid use of AQVESME in patients with cirrhosis (Child-Pugh Class A, B or C). ( 8.6 ) 8.1 Pregnancy Risk Summary Available data from clinical trials of AQVESME are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, mitapivat orally administered twice daily to pregnant rats and rabbits during organogenesis was not teratogenic at exposures up to 9.9- and 2.4‑fold the human exposure associated with the MRHD, respectively. Mitapivat administered orally to pregnant rats twice daily during organogenesis through lactation did not result in adverse developmental effects at doses up to 9.9 times the MRHD ( see Data) . The estimated background risk of major birth defects for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal Risk Transfusion requirements in thalassemia patients are increased during pregnancy.

Metabolism

The population pharmacokinetic model simulated C max , C trough , AUC 0-12 and accumulation ratio of mitapivat at the recommended dosage is listed in Table 3. Table 3: Steady State Mitapivat Exposure at the Recommended Dosage a Mitapivat Dosage C max (ng/mL) C trough (ng/mL) AUC 0-12 (ng*h/mL) Accumulation Ratio 100 mg twice daily b 1641.7 (12.9%) 71 (18.5%) 4835.6 (5.8%) 0.83 a Pharmacokinetic parameters are presented as geometric mean (CV%).

• Feb 17, 2022NDANDA216196Agios Pharms Inc

1. 1Haemoglobin Decreased19227%
2. 2Product Dose Omission Issue10014%
3. 3Fatigue9313%
4. 4Off Label Use628.6%
5. 5Arthralgia577.9%
6. 6Headache486.6%
7. 7Drug Ineffective466.4%
8. 8Malaise395.4%
9. 9Back Pain385.3%
10. 10Dyspnoea344.7%
11. 11Product Dose Omission In Error314.3%
12. 12Covid-19283.9%
13. 13Pain283.9%
14. 14Asthenia273.7%
15. 15Product Use Issue263.6%

The 10 most recently updated of 29 ClinicalTrials.gov registrations naming Mitapivat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease
  Active not recruiting · Observational · 6 enrolled · National Heart, Lung, and Blood Institute (NHLBI)
  NCT05675436updated 2026-06-11
• A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Not Regularly Transfused, Followed by a 5-Year Extension Period
  Active not recruiting · Phase 3 · Interventional · 30 enrolled · Agios Pharmaceuticals, Inc.
  NCT05175105updated 2026-06-01
• A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT)
  Active not recruiting · Phase 3 · Interventional · 258 enrolled · Agios Pharmaceuticals, Inc.
  NCT04770779updated 2026-06-01
• A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Regularly Transfused, Followed by a 5-Year Extension Period
  Active not recruiting · Phase 3 · Interventional · 49 enrolled · Agios Pharmaceuticals, Inc.
  NCT05144256updated 2026-06-01
• A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)
  Active not recruiting · Phase 3 · Interventional · 194 enrolled · Agios Pharmaceuticals, Inc.
  NCT04770753updated 2026-06-01
• A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With α- or β-Non-Transfusion-Dependent Thalassemia
  Not yet recruiting · Phase 3 · Interventional · 45 enrolled · Agios Pharmaceuticals, Inc.
  NCT07517133updated 2026-05-29
• A Study Evaluating the Efficacy and Safety of Mitapivat (AG-348) in Participants With Sickle Cell Disease (RISE UP)
  Active not recruiting · Phase 2 · Phase 3 · Interventional · 286 enrolled · Agios Pharmaceuticals, Inc.
  NCT05031780updated 2026-05-29
• A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT)
  Not yet recruiting · Phase 3 · Interventional · 54 enrolled · Agios Pharmaceuticals, Inc.
  NCT07506863updated 2026-05-29
• Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 15 enrolled · National Heart, Lung, and Blood Institute (NHLBI)
  NCT04610866updated 2026-05-05
• A Study of AG-348 in Adult Participants With Pyruvate Kinase (PK) Deficiency
  Completed · Phase 2 · Interventional · 52 enrolled · Agios Pharmaceuticals, Inc.
  NCT02476916updated 2026-05-01

Frequently asked questions

How does Mitapivat work?

Mitapivat is a pyruvate kinase activator that acts by allosterically binding to the pyruvate kinase tetramer and increasing pyruvate kinase (PK) activity. Imbalances in globin chain production during erythropoiesis result in increased oxidative stress, which leads to ineffective erythropoiesis and hemolysis.

What is Mitapivat used for?

According to FDA labeling, Mitapivat carries indications including: AQVESME is indicated for the treatment of anemia in adults with alpha- or beta-thalassemia. AQVESME is a pyruvate kinase activator indicated for the treatment of anemia in adults with alpha- or beta-thalassemia.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Mitapivat?

Mitapivat is classified as Other hematological agents, Pyruvate Kinase Activator, Cytochrome P450 2B6 Inducers, Cytochrome P450 2C19 Inducers, Cytochrome P450 2C8 Inducers, Cytochrome P450 2C9 Inducers, Cytochrome P450 3A Inducers, P-Glycoprotein Inhibitors, Pyruvate Kinase Activators, UGT1A1 Inducers.

What are the brand names for Mitapivat?

Mitapivat is marketed under brand names including Aqvesme, Pyrukynd.

What are the contraindications for Mitapivat?

Mitapivat labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.