How Do Pyruvate Kinase Activators Work?

Pyruvate kinase activators are medications used to treat hemolytic anemia in adult patients with pyruvate kinase deficiency. Pyruvate kinase deficiency is a rare genetic blood disorder that is characterized by premature destruction (hemolysis) of red blood cells (RBCs) that results in lifelong hemolytic anemia.

Pyruvate kinase is an enzyme involved in the generation of adenosine triphosphate (ATP), a molecule that stores and provides energy in the form that cells can use for their survival and functions. In patients with pyruvate kinase deficiency, the specific isoform of pyruvate kinase (PK-R) that RBCs use for energy is mutated, leading to reduced ATP production, reduced RBC survival and chronic hemolysis.

Pyruvate kinase activators bind to pyruvate kinase tetramer and increase pyruvate kinase activity, increasing ATP production and prolonging RBC survival. Pyruvate kinase activators activate both mutated and normal pyruvate kinases.

Currently, the first and only pyruvate kinase activator is mitapivat, approved by the FDA in February 2022. Mitapivat is also being investigated for use in other hereditary red blood cell disorders associated with hemolytic anemia, including sickle cell disease and alpha and beta thalassemia.

Pyruvate kinase activators are oral tablets approved by the FDA to treat hemolytic anemia in adults with pyruvate kinase deficiency.

Side effects of pyruvate kinase activators may include the following:

• Decreased estrone in males
• Decreased estradiol in males
• Increase in urate levels
• Back pain
• Joint pain (arthralgia)
• Musculoskeletal pain
• Rib fracture
• Mouth and throat pain (oropharyngeal pain)
• Hot flush
• Gastroenteritis
• High levels of triglycerides in the blood (hypertriglyceridemia)
• Increase in blood testosterone in males
• High blood pressure (hypertension)
• Irregular heart rhythm (arrhythmia)
• Irregular and rapid atrial contractions (atrial fibrillation)
• Dry mouth
• Constipation
• Breast discomfort and pain (mastalgia)
• Abnormal skin sensations (paresthesia)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of pyruvate kinase activators include:

• mitapivat
• Pyrukynd