ACTIVATE-T: PATIENTS WHO WERE REGULARLY TRANSFUSED

PYRUKYND® (mitapivat) delivered clinically meaningful transfusion reductions1

See ACTIVATE-T Study Design

33% (n=9) of patients receiving PYRUKYND met the key endpoint of
having a 33% reduction in RBC units2

33% OF PATIENTS HAD A ≥33% REDUCTION IN RBC UNITS2

33% of patients
  • Clinically meaningful transfusion reduction response was defined as a ≥33% reduction in the number of RBC units transfused over 24 weeks compared to historical transfusion burden1

PYRUKYND gave some patients the opportunity to eliminate transfusions2

transfusion icon with a struck-through cricle

22% of patients (6) achieved
transfusion-free status2*

during the 24-week fixed-dose
period (95% CI: 9, 42)1

one purple blood drop icon and one teal blood drop icon with a plus over a purple upwards arrow

11% of patients (3) achieved Hb concentrations in the normal range1,3†

at least once ≥8 weeks after
transfusion in the 24-week fixed-dose period (95% CI: 2, 29)1

All patients who achieved transfusion-free status have continued to be transfusion free in the ongoing long-term extension study, with follow-up ranging from 50 to 95 weeks4

ACTIVATE-T CLINICAL STUDY DETAILS

STUDY DESIGN1,2

chart illustrating the ACTIVATE-T study design, from screening, to individualized dose optimization period, to fixed-dose period, ending with long-term extension chart illustrating the ACTIVATE-T study design, from screening, to individualized dose optimization period, to fixed-dose period, ending with long-term extension

KEY ELIGIBILITY CRITERIA

  • Patients were included if they had documented presence of at least 2 variant alleles in the PKLR gene, of which at least 1 was a missense variant2
  • Patients who were homozygous for the c.1436G>A (p.R479H) variant or had 2 non-missense variants (without the presence of another missense variant) in the PKLR gene were excluded2

KEY EFFICACY ENDPOINT

  • Transfusion reduction response, defined as ≥33% reduction in the number of RBC units transfused during the 24-week fixed-dose period vs historical transfusion burden2

LONG-TERM EXTENSION STUDY

  • The long-term extension study is ongoing with transfusion reduction data currently out to 21.9 months4

ACTIVATE-T: BASELINE CHARACTERISTICS1,2

PATIENT DEMOGRAPHICS

  • The median patient age was 36 years (range: 18-68 years)
  • 20 patients (74%) had the missense/missense PKLR gene variant, and 7 patients (26%) had the missense/non-missense PKLR gene variant
  • 21 patients (78%) had a history of splenectomy
  • Patients with splenectomy, cholecystectomy, or elevated ferritin levels were included in the study

TRANSFUSIONS

  • Patients had a median of 9 transfusion episodes (range: 6-17) in the 52 weeks before the first dose of PYRUKYND and a median of 4 episodes (range: 2.8-7.8) standardized to 24 weeks
  • Patients had a median of 15 RBC units (range: 6-44) in the 52 weeks before the first dose of PYRUKYND and a median of 7 red blood cell units transfused (range: 3-20) standardized to 24 weeks

HEMOGLOBIN (g/dL)

  • The median baseline Hb was 9.1 g/dL (range: 7.4-10.9 g/dL)

EVIDENCE OF COMPLICATIONS & COMORBIDITIES ASSOCIATED WITH PK DEFICIENCY

  • Iron overload (median baseline ferritin was 1324 ug/L; range: 163-5357 ng/mL)
  • Chelation therapy use in the year before the first dose of study treatment in 24 patients (89%)
  • Decreased bone mineral density in 20 patients (74%) who had a baseline femoral neck or lumbar spine T-score <-1.0
  • History of cholecystectomy in 23 patients (85%)

Hb=hemoglobin; RBC=red blood cell.

CI is based on Clopper-Pearson Method.2

*The median duration of response for the 6 patients was 17 months (range 11.5+, 21.8+).

†Normal range in Hb concentration is 13.0-15.0 g/dL for men and 11.6-13.5 g/dL for women.3

‡Screening may have been extended beyond 8 weeks if there was a delay in obtaining a patient’s complete transfusion history or to ensure that the first dose of study drug could be administered 2 to 7 days after the most recent transfusion.1

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See the demonstrated safety profile of PYRUKYND across
multiple clinical studies

REVIEW SAFETY

Learn about dosing and administration of PYRUKYND

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References: 1. Data on file. Agios Pharmaceuticals, Inc. 2. PYRUKYND. Prescribing information. Agios Pharmaceuticals, Inc.; 2022. 3. Grace RF, Rose C, Layton DM, et al. Safety and efficacy of mitapivat in pyruvate kinase deficiency. N Engl J Med. 2019;381(10):933-944. 4. 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.

Indication

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.

Drug Interactions:

  • 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.

Indication

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.

Indication

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.

Drug Interactions:

  • 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.

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