Last reviewed 2026-04-20 · How we verify

Pyrukynd (MITAPIVAT)

Pyrukynd works by activating the pyruvate kinase PKLR enzyme to improve energy production in red blood cells.

Pyrukynd (MITAPIVAT) is a small molecule pyruvate kinase activator developed by Agios Pharmaceuticals Inc, now owned by Agios Pharms Inc. It targets the pyruvate kinase PKLR enzyme to treat pyruvate kinase (PK) deficiency. Pyrukynd was FDA-approved in 2022 for this indication. It is a patented medication with no generic manufacturers available. As a pyruvate kinase activator, Pyrukynd works by enhancing the activity of the PKLR enzyme, which is deficient in patients with PK deficiency.

At a glance

Mechanism of action

Mitapivat is pyruvate kinase activator that acts by allosterically binding to the pyruvate kinase tetramer and increasing pyruvate kinase (PK) activity. The red blood cell (RBC) form of pyruvate kinase (PK-R) is mutated in PK deficiency, which leads to reduced adenosine triphosphate (ATP), shortened RBC lifespan, and chronic hemolysis.

Approved indications

• Pyruvate kinase (PK) deficiency

Boxed warnings

• 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 [see Warnings and Precautions ( 5.1 )] . 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 [see Warnings and Precautions ( 5.2 )] . WARNING: HEPATOCELLULAR INJURY See full prescribing information for complete boxed warning. 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 hepatocellular injury is suspected. ( 5.1 ) AQVESME is available only through a restricted program called the AQVESME REMS. ( 5.2 )

Common side effects

• Back pain
• Increased urate
• Hypertriglyceridemia
• Gastroenteritis
• Hot flush
• Oropharyngeal pain
• Arrhythmia
• Breast discomfort
• Constipation
• Dry mouth
• Paresthesia
• Atrial fibrillation

Key clinical trials

• Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease
• A Study Evaluating the Efficacy and Safety of Mitapivat (AG-348) in Participants With Sickle Cell Disease (RISE UP) (PHASE2,PHASE3)
• A Study of Mitapivat in Participants With Sickle Cell Disease and Nephropathy (PHASE2)
• 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 (PHASE3)
• A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT) (PHASE3)
• A Study to Provide Continued Access to Mitapivat for Participants Who Previously Completed an Agios-Sponsored Mitapivat Study (PHASE4)
• A Study to Determine the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of AG-348 in Adult Participants With Non-transfusion-dependent Thalassemia (PHASE2)
• A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT) (PHASE3)

Patents

Primary sources

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