General Information

Pyrukynd (mitapivat) is a pyruvate kinase activator.

Pyrukynd is specifically indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.

Pyrukynd is supplied as tablets for oral administration. Pyrukynd can be taken with or without food and swallowed whole. Do not split, crush, chew, or dissolve the tablets.

• The starting dosage is 5 mg orally twice daily. To gradually increase hemoglobin (Hb), titrate Pyrukynd from 5 mg twice daily to 20 mg twice daily, and then to the maximum recommended dose of 50 mg twice daily, with these dose increases occurring every 4 weeks.
• Assess Hb and transfusion requirement before increasing to the next dose level, as some patients may reach and maintain normal Hb at 5 mg twice daily or 20 mg twice daily.
• Discontinue Pyrukynd if no benefit has been observed by 24 weeks, based on the hemoglobin and hemolysis laboratory results and transfusion requirements.

Mechanism of Action

Pyrukynd (mitapivat) is a 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.

Side Effects

Adverse effects associated with Pyrukynd may include, but are not limited to, the following:

• estrone decreased (males)
• increased urate
• back pain
• estradiol decreased (males)
• arthralgia 

Clinical Trial Results

FDA approval was based on the results from two pivotal studies, ACTIVATE and ACTIVATE-T, conducted in not regularly transfused and regularly transfused adults with PK deficiency, respectively. Both trials met the primary endpoints. For ACTIVATE: Pyrukynd demonstrated a statistically significant increase in hemoglobin in patients with PK deficiency who are not regularly transfused. 40 percent (n=16) of patients randomized to Pyrukynd achieved a hemoglobin response, compared to 0 patients randomized to placebo. For ACTIVATE-T: Pyrukynd demonstrated a statistically significant and clinically meaningful reduction in transfusion burden for patients who are regularly transfused. 33 percent (n=9) of patients achieved a transfusion reduction response, defined as a ≥33% reduction in transfusion burden in the 24-week fixed dose period compared with individual historical transfusion burden standardized to 24 weeks. 22 percent (n=6) of patients were transfusion-free during the fixed-dose period.