Earlier this year, the U.S. Food and Drug Administration (FDA) approved mitapivat (PYRUKYND) for the treatment of patients with hemolytic anemia due to pyruvate kinase deficiency (PKD). According to 2 Minute Medicine, a Phase 3 clinical trial sought to understand the safety, efficacy, and tolerability of mitapivat – compared to a placebo – in those with PKD who were not receiving red blood cell transfusions on a regular basis. 

The study found that mitapivat was both safe and effective, particularly when compared with a placebo. Additionally, though some patients within the trial did experience adverse reactions to treatment, no patients dropped out from the study due to these reactions. 

Mitapivat: An Overview

In an unrelated article published in Therapeutic Advancements in Hematology, the authors describe mitapivat as:

a novel, first-in-class oral small molecule allosteric activator of the pyruvate kinase enzyme. Mitapivat has been shown to significantly upregulate both wild-type and numerous mutant forms of erythrocyte pyruvate kinase (PKR), increasing adenosine triphosphate (ATP) production and reducing levels of 2,3-diphosphogylcerate.

Within this particular Phase 3 clinical study, researchers evaluated mitapivat versus a placebo for individuals with PKD. Altogether, 80 adult patients enrolled in the trial. Participants received either an escalating mitapivat dose 2x daily or a placebo for up to 24 weeks. After this period, all patients were able to participate in an extension trial where they would all receive treatment. Findings from the study include:

• 40% (32 patients) saw heightened hemoglobin levels, highlighting the potential of mitapivat in treating hemolytic anemia. Alternately, 0% of those receiving the placebo saw improvement. 
• Those receiving mitapivat also saw improved hemolysis. Hemolysis is the destruction of red blood cells. Therefore, those using mitapivat had less red blood cell destruction. 
• Some side effects and adverse reactions did occur, including a number of serious reactions. However, the most common reactions were headaches and nausea. 

About Pyruvate Kinase Deficiency (PKD)

Pyruvate kinase deficiency, known as PKD or PK deficiency, is a rare disorder caused by PKLR gene mutations. These mutations, inherited in an autosomal recessive pattern, cause a deficiency of pyruvate kinase, an enzyme. In turn, this causes adenosine triphosphate (ATP) deficiency, which results in abnormal red blood cells and hemolytic anemia. An estimated 1 in every one million people has PKD, although the incidence could be higher. PKD is a variable condition. Some individuals may experience mild symptoms while others may experience life-threatening symptoms. When symptoms appear, these can include:

• Fetal hydrops (fluid buildup within fetal tissues and organs – noticed before birth)
• Jaundice (yellowing of the skin, eyes, and mucus membranes) in infants
• Hemolytic anemia
• Kernicterus (in infants)
• Enlarged spleen
• Pallor (extremely pale skin)
• Gallstones
• Fatigue and general malaise
• Headache
• Irritability
• Weakened bones
• Pulmonary hypertension
• Shortness of breath and/or difficulty breathing
• Iron overload