Introducing the First and Only Disease-Modifying Treatment for Pyruvate Kinase (PK) Deficiency1
PYRUKYND is an allosteric activator of PK that increases the activity of the PK enzyme, improving glycolytic function and ATP in healthy volunteers.
ACTIVATE Trial Design
ACTIVATE: A 24-week, randomized, placebo-controlled clinical study assessed the Hb response and safety of PYRUKYND in patients with a presence of at least 2 variant alleles in the PKLR gene, of which at least one was a missense variant, and who did not receive regular transfusions.
Key efficacy endpoint
- Clinically meaningful Hb response (≥1.5 g/dL increase from baseline) in ≥2 assessments over the 12-week fixed-dose period (weeks 16, 20, and 24 without transfusions)1
- The long-term extension study is ongoing with Hb response data currently out to 19.5 months2
Learn about the first phase 3 pivotal trial program for PK deficiency.1Discover the clinical results
Mechanism of Action
Target the underlying cause of PK deficiency with PYRUKYND1,3
PYRUKYND is an allosteric activator of pyruvate kinase that increases activity of PK enzyme, and has been shown to improve glycolytic function and ATP production in healthy volunteers.1,3,4
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ATP=adenosine triphosphate; Hb=hemoglobin; LDH=lactate dehydrogenase; RBC=red blood cell.
*PYRUKYND showed statistically significant improvements in Hb, indirect bilirubin, reticulocytes, LDH, and haptoglobin relative to placebo.1,3
REFERENCES: 1. PYRUKYND. Prescribing information. Agios Pharmaceuticals, Inc.; 2022. 2. Grace RF, Glenthøj A, Barcellini W, et al. Durability of hemoglobin response and reduction in transfusion burden is maintained over time in patients with pyruvate kinase deficiency treated with mitapivat in a long-term extension study. Presented at: American Society of Hematology Annual Meeting; December 11-14, 2021; Atlanta, GA. https://ash.confex.com/ash/2021/webprogram/Paper147711.html. Accessed January 9, 2022. 3. Rab MAE, van Oirschot BA, Kosinski PA, et al. AG-348 (mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica. 2021;106(1):238-249. 4. Kung C, Hixon J, Kosinski PA, et al. AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency. Blood. 2017;130(11):1347-1356.
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.
IMPORTANT SAFETY INFORMATION
Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.
Adverse Reactions: Serious adverse reactions occurred in 10% of patients receiving PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which occurred in 1 patient. In the ACTIVATE trial, the most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia.
- Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
- Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
- Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
- Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
- UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
- P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.
Please see full Prescribing Information for PYRUKYND.
This program is not intended as medical advice and patients should consult their healthcare team with questions related to their treatment.