Continued Access to Mitapivat for Pyruvate Kinase Deficiency

Enrolling by invitation at 7 trial locations

Overseen By Agios Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Agios Pharmaceuticals, Inc.

Must be taking: Mitapivat

Disqualifiers: Allergy to mitapivat, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to end of treatment period

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to provide ongoing access to mitapivat for individuals with pyruvate kinase deficiency, a condition affecting red blood cells that can cause anemia. The trial focuses on participants who previously benefited from mitapivat in another study but cannot access it commercially, often due to country-specific regulations. Those who completed a related mitapivat study and found it helpful might be suitable candidates, especially if commercial access is unavailable. As a Phase 4 trial, this study involves a treatment already FDA-approved and proven effective, aiming to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

What is the safety track record for this treatment?

Research shows that mitapivat is generally well-tolerated by patients with pyruvate kinase deficiency. A previous study found common side effects included some lab test changes, such as lower levels of the hormone estrone in males. Serious side effects, like hemolytic anemia (the rapid breakdown of red blood cells) and pharyngitis (a sore throat), were rare, occurring in only 4% of patients.

Additionally, mitapivat quickly increased hemoglobin levels in about half of the patients, which is a positive outcome. These findings suggest that mitapivat is relatively safe, especially since the FDA has already approved it for treating this condition. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Mitapivat is unique because it targets pyruvate kinase deficiency by activating the pyruvate kinase enzyme in red blood cells. This is different from traditional treatments like blood transfusions or splenectomy, which manage symptoms rather than addressing the underlying cause. Researchers are excited about mitapivat because it has the potential to improve hemoglobin levels and reduce the need for transfusions, offering a more direct and effective option for patients.

What is the effectiveness track record for mitapivat in treating pyruvate kinase deficiency?

Research has shown that mitapivat, the treatment under study in this trial, effectively treats pyruvate kinase deficiency. Studies have found that mitapivat significantly raises hemoglobin levels, which are crucial for oxygen transport in the blood. It also reduces hemolysis, the rapid breakdown of red blood cells. Many patients have reported feeling less tired and weak, indicating improvements in anemia symptoms. Over several years, mitapivat has proven both safe and effective, offering lasting benefits for those with this condition. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals who have completed a previous Agios-sponsored study on mitapivat and benefited from it, but can't get the drug commercially due to regulations or access issues. They must agree to use two forms of contraception if applicable, not join other studies, and comply with all procedures.

Inclusion Criteria

Is unable to obtain mitapivat treatment due to country regulations or lack of commercial access

Written informed consent from the participant before any study-related procedures are conducted and willing to comply with all study procedures for the duration of the study

For women of childbearing potential, must be abstinent of sexual activities that may result in pregnancy as part of their usual lifestyle or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of providing informed consent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can be an acceptable barrier method

Exclusion Criteria

Participants with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor)

I am not allergic to mitapivat or its components.

Participants who are institutionalized by regulatory or court order

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue the mitapivat dose regimen they were receiving at the final visit of their antecedent study

Up to end of treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 6.2 years

What Are the Treatments Tested in This Trial?

Interventions

• Mitapivat

Trial Overview The trial provides continued access to mitapivat for participants with hemolytic anemia or pyruvate kinase deficiency who previously responded well in an earlier study but lack commercial access to the medication.

How Is the Trial Designed?

Group I: Mitapivat Experimental Treatment 1 Intervention

Participants will receive mitapivat of 5, 20 or 50 milligrams (mg), orally, twice daily (BID), based on the last dose received by the participants in the antecedent study. Mitapivat will be administered from Day 1 up to end of treatment period of this study.

Who Is Running the Clinical Trial?

Agios Pharmaceuticals, Inc.

Lead Sponsor

Trials

55

Recruited

4,200+

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2116634

Mitapivat versus Placebo for Pyruvate Kinase Deficiency In patients with pyruvate kinase deficiency, mitapivat significantly increased the hemoglobin level, decreased hemolysis, and improved patient- ...

2. investor.agios.com investor.agios.com/static-files/af4512cc-c513-45ac-977a-49bccae1c139

Clinically meaningful improvements in patient‐reported ... Mitapivat, a first-in-class, oral activator of PK approved for adults with PK deficiency4 has demonstrated improvements in anemia and.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31483964/

Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency Conclusions: The administration of mitapivat was associated with a rapid increase in the hemoglobin level in 50% of adults with pyruvate kinase ...

4. agios.com agios.com/agios-eha-2025-data-room/

Agios EHA 2025 Data Room In the study, mitapivat showed sustained efficacy and tolerability over three years, including improvements in anemia, hemolysis, painful vaso-occlusive crises, ...

5. ashpublications.org ashpublications.org/bloodrci/article/1/2/100014/546279/Long-term-mitapivat-treatment-is-safe-and

Long-term mitapivat treatment is safe and efficacious in ... Median of 2.53-year follow-up of mitapivat showed favorable safety and tolerability in patients with SCD. Sustained improvements in Hb, ...

6. pyrukynd.com pyrukynd.com/hcp/pyrukynd-safety/

Safety Profile | PYRUKYND® (mitapivat) tablets Adverse Reactions: The most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1902678

Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency The administration of mitapivat was associated with a rapid increase in the hemoglobin level in 50% of adults with pyruvate kinase deficiency.

8. investor.agios.com investor.agios.com/news-releases/news-release-details/agios-phase-3-activate-kids-study-mitapivat-children-pyruvate

Agios' Phase 3 ACTIVATE-Kids Study of Mitapivat in ... The ACTIVATE-Kids Phase 3 study of mitapivat in children aged 1 to <18 years with PK deficiency who are not regularly transfused achieved its primary endpoint ...

9. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/3512/428360/Long-Term-Safety-and-Efficacy-of-Mitapivat-AG-348

Long-Term Safety and Efficacy of Mitapivat (AG-348), a ... These long-term data support the potential of mitapivat as the first disease-altering therapy for PK deficiency. Two phase 3 trials are underway ...