What side effects are associated with this type of intervention?

The most common side effects of Mitapivat, a treatment for Alpha-Thalassemia that activates pyruvate kinase to improve red blood cell function and increase hemoglobin levels, include initial insomnia, dizziness, and headache. A serious adverse event reported was grade 3 renal impairment, though it was considered unrelated to the drug. These side effects should be considered when assessing the treatment's safety and efficacy.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Alpha-Thalassemia that function similarly to Mitapivat, which activates pyruvate kinase to improve red blood cell function and increase hemoglobin levels. Current treatments for Alpha-Thalassemia primarily focus on managing symptoms and complications, such as regular blood transfusions and iron chelation therapy to manage iron overload. The study of Mitapivat represents a novel approach in the treatment of non-transfusion-dependent thalassemia by targeting the underlying metabolic pathways to improve red blood cell function and increase hemoglobin levels.

What other types of research exist?

Promising novel alternatives to Mitapivat for Alpha-Thalassemia patients include gene therapy approaches such as CRISPR-Cas9 mediated gene editing, which aims to correct the genetic mutations causing thalassemia. Additionally, luspatercept, a TGF-beta superfamily ligand trap, has shown potential in increasing hemoglobin levels by enhancing erythroid maturation. Other emerging treatments include erythropoiesis-stimulating agents like Hematide, which is being evaluated for its efficacy in treating anemia associated with chronic conditions.

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Activator of Pyruvate Kinase-R

Mitapivat for Thalassemia (ENERGIZE Trial)

Phase 3

Waitlist Available

Research Sponsored by Agios Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Non-transfusion-dependent, defined as ≤5 red blood cell (RBC) units during the 24-week period before randomization; and no RBC transfusions ≤8 weeks before providing informed consent and no RBC transfusions during the Screening Period

Documented diagnosis of thalassemia (β-thalassemia with or without α-globin gene mutations, hemoglobin E (HbE)/β-thalassemia, or α-thalassemia/hemoglobin H [HbH] disease) based on Hb electrophoresis, Hb high-performance liquid chromatography (HPLC)), and/or deoxyribonucleic acid (DNA) analysis

Must not have

Known allergy to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, and magnesium stearate, Opadry® II Blue [hypromellose, titanium dioxide, lactose monohydrate, triacetin, and FD&C Blue #2])

Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥18 weeks before randomization

Timeline

Screening 3 weeks

Treatment Varies

Follow Up weeks 12, 16, 20, and 24

Awards & highlights

Pivotal Trial

Summary

This trial is testing mitapivat, a drug that may help improve anemia by making red blood cells healthier and last longer. It targets patients with a specific type of thalassemia who don't need regular blood transfusions but still suffer from anemia.

Who is the study for?

This trial is for individuals with alpha- or beta-non-transfusion dependent thalassemia (NTDT) who have stable hemoglobin levels ≤10.0 g/dL and haven't had more than 5 blood transfusions in the past 24 weeks. Participants must not be pregnant, breastfeeding, or have certain other health conditions like uncontrolled heart disease, severe kidney issues, or active infections.

What is being tested?

The study is testing Mitapivat against a placebo to see if it helps improve anemia in people with NTDT. Patients will either receive the actual drug or a placebo that has no therapeutic effect to compare outcomes between the two groups.

What are the potential side effects?

While specific side effects of Mitapivat are not listed here, common side effects may include reactions at the site of administration, potential liver enzyme elevations, fatigue, headache, and digestive discomfort.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have not needed more than 5 blood transfusions in the last 6 months and none in the last 2 months.

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I have been diagnosed with thalassemia based on specific blood tests or DNA analysis.

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My hydroxyurea dose has been the same for at least 16 weeks.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am allergic to mitapivat or its ingredients.

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I haven't had blood cell boosters in the last 18 weeks.

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I have not taken strong CYP3A4/5 inhibitors or inducers for the required time before joining.

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My kidney function is reduced, with an eGFR below 45 mL/min/1.73m^2.

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I have a documented history of sickle cell disease.

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I have had gene therapy or a bone marrow/stem cell transplant before.

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I haven't taken anabolic steroids in the last 4 weeks, but I may be on stable testosterone treatment for low testosterone.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ weeks 12, 16, 20, and 24

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~weeks 12, 16, 20, and 24

This trial's timeline: 3 weeks for screening, Varies for treatment, and weeks 12, 16, 20, and 24 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants With Hemoglobin (Hb) Response

Secondary study objectives

Change From Baseline in Average Functional Assessment of Chronic Illness Therapy (FACIT) -Fatigue Subscale Score from Week 12 through Week 24

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), Graded by Severity

Percentage of Participants With Hb 1.5+ Response

+2 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: MitapivatExperimental Treatment1 Intervention

Double-blind Period: Participants will receive mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks. Open-label Extension Period: Participants who do not discontinue study drug may choose to continue to receive mitapivat for up to an additional 5 years after the Double-blind Period.

Group II: PlaceboPlacebo Group2 Interventions

Double-blind Period: Participants will receive placebo matching mitapivat, orally, BID for 24 weeks. Open-label Extension Period: Participants who do not discontinue study drug may choose to receive mitapivat for up to an additional 5 years after the Double-blind Period.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Mitapivat

2023

Completed Phase 1

~20

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Alpha-Thalassemia aim to improve red blood cell function and increase hemoglobin levels. Mitapivat, an oral pyruvate kinase activator, enhances the activity of pyruvate kinase, an enzyme crucial for red blood cell metabolism, leading to improved red blood cell function and increased hemoglobin levels. This is particularly important for Alpha-Thalassemia patients as it helps alleviate anemia and reduces the need for blood transfusions, thereby improving their quality of life. Other treatments, such as hydroxyurea, increase fetal hemoglobin production, which can also ameliorate symptoms by reducing the proportion of defective hemoglobin. These mechanisms are vital as they directly address the underlying issues of ineffective erythropoiesis and hemolysis in Alpha-Thalassemia.

Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in adults with non-transfusion dependent α-thalassaemia or β-thalassaemia: an open-label, multicentre, phase 2 study.Possible effects of sirolimus treatment on the long‑term efficacy of COVID‑19 vaccination in patients with β‑thalassemia: A theoretical perspective.