CLINICAL TRIALS PROFILE FOR MITAPIVAT SULFATE

All Clinical Trials for mitapivat sulfate

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03991312 ↗	Study to Evaluate the Effect of Multiple Doses of Itraconazole and Rifampin on the Single-Dose Pharmacokinetics of Mitapivat Sulfate (AG-348) in Healthy Adult Participants	Completed	Agios Pharmaceuticals, Inc.	Phase 1	2019-06-20	Part 1 of this study will determine the effect of multiple-dose itraconazole, a strong cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) inhibitor, on the single-dose pharmacokinetic(s) (PK) of mitapivat sulfate in healthy adult participants. Part 2 of this study will determine the effect of multiple-dose rifampin, a strong CYP3A4 and P-gp inducer, on the single-dose pharmacokinetic(s) (PK) of mitapivat sulfate in healthy adult participants.
NCT04000165 ↗	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Multiple Oral Doses of AG-348 in Subjects With Stable Sickle Cell Disease	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Early Phase 1	2019-07-11	Background: Sickle Cell Disease (SCD) is an inherited blood disorder. People with SCD have abnormal hemoglobin in their red blood cells. Researchers are investigating the safety and efficacy of an investigational medicine called AG-348 (mitapivat sulfate) to determine if it will help people with SCD. Objective: To test the tolerability and safety of AG-348 in people with SCD. Eligibility: People ages 18 and older with SCD. Design: Participants will have 8 visits over approximately 14 weeks. At the first visit participants will be screened with a medical history; a physical exam; and blood, urine, and heart tests. At the following 5 visits participants will stay at the clinic for 1 night each. Participants will take study drug in increasing doses upto visit 6, after which the drug will be tapered off. All visits will include physical exam, blood, and urine tests. The last visit will occur 4 weeks after stopping the drug and also includes a heart test. Participants will provide DNA from the blood samples they provide. The DNA will be tested for an inherited gene that can cause differences in response to the study drug. Researchers may also test other genes to see if they can find any genes that interact with SCD.
NCT04000165 ↗	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Multiple Oral Doses of AG-348 in Subjects With Stable Sickle Cell Disease	Completed	National Institutes of Health Clinical Center (CC)	Early Phase 1	2019-07-11	Background: Sickle Cell Disease (SCD) is an inherited blood disorder. People with SCD have abnormal hemoglobin in their red blood cells. Researchers are investigating the safety and efficacy of an investigational medicine called AG-348 (mitapivat sulfate) to determine if it will help people with SCD. Objective: To test the tolerability and safety of AG-348 in people with SCD. Eligibility: People ages 18 and older with SCD. Design: Participants will have 8 visits over approximately 14 weeks. At the first visit participants will be screened with a medical history; a physical exam; and blood, urine, and heart tests. At the following 5 visits participants will stay at the clinic for 1 night each. Participants will take study drug in increasing doses upto visit 6, after which the drug will be tapered off. All visits will include physical exam, blood, and urine tests. The last visit will occur 4 weeks after stopping the drug and also includes a heart test. Participants will provide DNA from the blood samples they provide. The DNA will be tested for an inherited gene that can cause differences in response to the study drug. Researchers may also test other genes to see if they can find any genes that interact with SCD.
NCT04472832 ↗	A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Mitapivat (AG-348) in Healthy Adult Participants	Completed	Agios Pharmaceuticals, Inc.	Phase 1	2020-06-17	This is a Phase 1, randomized, single-dose, double-blinded, 4-period, crossover study to evaluate the pharmacokinetics, safety, and tolerability of mitapivat in healthy adult participants under fasted and fed (high-fat meal) conditions. Secondary objectives include evaluating the effect of mitapivat on electrocardiogram (ECG) parameters, including concentration-QT interval corrected for heart rate (C-QTc) analysis under fasted conditions. The study will include a 28-day screening period, four 7-day treatment periods. Participants will receive a follow-up telephone call within 28 (±1) days after the last dose of study drug.
NCT04565678 ↗	A Study to Assess the Relative Bioavailability and Effect of Food on the Coated Granule Formulation of Mitapivat in Healthy Participants	Completed	Agios Pharmaceuticals, Inc.	Phase 1	2020-09-21	The primary purpose of this study is to assess the relative bioavailability of the mitapivat coated granule formulation compared to the tablet formulation following a single oral dose of mitapivat under fasted conditions in healthy adult participants.
NCT04696393 ↗	A Study to Compare the Pharmacokinetics and Safety of Mitapivat 100 mg Tablet Formulation With Mitapivat 2 × 50 mg Tablet Formulation in Healthy Adult Participants	Completed	Agios Pharmaceuticals, Inc.	Phase 1	2021-01-06	The primary purpose of this study is to characterize and compare the pharmacokinetic profiles of mitapivat following a single dose administration of 100 mg mitapivat in two tablet formulations (50 mg and 100 mg tablet strengths) in healthy adult participants.
NCT04770753 ↗	A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)	Recruiting	Agios Pharmaceuticals, Inc.	Phase 3	2021-11-01	The primary purpose of this study is to compare the effect of mitapivat versus placebo on anemia in participants with alpha- or beta-non-transfusion dependent thalassemia (NTDT).

Clinical Trial Conditions for mitapivat sulfate

Condition Name

Condition Name for mitapivat sulfate
Intervention	Trials
Healthy Volunteers	4
Sickle Cell Disease	2
Non-Transfusion-dependent Beta-Thalassemia	1
Pediatric Hemolytic Anemia	1

Condition MeSH

Condition MeSH for mitapivat sulfate
Intervention	Trials
Anemia, Hemolytic	3
Thalassemia	2
beta-Thalassemia	2
alpha-Thalassemia	2

Clinical Trial Locations for mitapivat sulfate

Trials by Country

Trials by Country for mitapivat sulfate
Location	Trials
United States	7
Canada	5
Netherlands	1
Denmark	1
Japan	1

Trials by US State

Trials by US State for mitapivat sulfate
Location	Trials
Texas	3
Massachusetts	2
Maryland	1
Arizona	1

Clinical Trial Progress for mitapivat sulfate

Clinical Trial Phase

Clinical Trial Phase for mitapivat sulfate
Clinical Trial Phase	Trials
PHASE2	1
Phase 4	1
Phase 3	4

Clinical Trial Status

Clinical Trial Status for mitapivat sulfate
Clinical Trial Phase	Trials
Not yet recruiting	6
Completed	5
RECRUITING	3

Clinical Trial Sponsors for mitapivat sulfate

Sponsor Name

Sponsor Name for mitapivat sulfate
Sponsor	Trials
Agios Pharmaceuticals, Inc.	12
National Heart, Lung, and Blood Institute (NHLBI)	2
National Institutes of Health Clinical Center (CC)	1

Sponsor Type

Sponsor Type for mitapivat sulfate
Sponsor	Trials
Industry	12
NIH	3
Other	2

Clinical Trials Update, Market Analysis, and Projection for Mitapivat Sulfate

Last updated: October 28, 2025

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Introduction

Mitapivat sulfate (AG-348) emerges as a promising pharmacological agent targeting disorders involving abnormal hemolysis, such as pyruvate kinase deficiency (PKD) and sickle cell disease (SCD). Its mechanism, centered on activating pyruvate kinase-R (PKR), enhances glycolytic flux, subsequently improving red blood cell (RBC) lifespan and reducing hemolytic anemia. With an accelerating pipeline, recent clinical trials, and a growing unmet medical need, understanding mitapivat sulfate’s development trajectory and market potential is imperative for stakeholders.

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Clinical Trials Update

Phase I and II Development

Mitapivat sulfate's clinical journey began with early-phase trials evaluating safety, pharmacokinetics, and dosing. In Phase I studies, safety profiles were favorable, with minimal adverse events observed at therapeutic doses (reference [1]). Subsequent Phase II trials assessed efficacy in PKD and SCD populations.

Key Phase II Outcomes

In patients with PKD, mitapivat sulfate demonstrated significant hemoglobin improvements, with some subjects achieving transfusion independence. Notably, the ACTIVATE trial reported a median increase in hemoglobin of approximately 1-2 g/dL over baseline, with durable effects observed over several months (reference [2]). Similarly, in SCD studies, preliminary data indicated reductions in vaso-occlusive events and hemolytic markers.

Ongoing and Recent Trials

• Phase III Trials: The pivotal Activ-350 trial is evaluating the efficacy and safety of mitapivat sulfate in adults with PKD, with primary endpoints focusing on transfusion avoidance and hemoglobin stabilization. Results are anticipated within the next 12-18 months, with initial data suggesting positive trends.

• Extended Indications: Current studies are exploring mitapivat sulfate in other hemolytic anemias, including thalassemia and other rare inherited disorders, broadening its therapeutic scope.

• Regulatory Status: The developer, Agios Pharmaceuticals, submitted a BREAKTHROUGH THERAPY designation application for PKD, acknowledging early clinical promise and streamlining future approval pathways (reference [3]).

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Market Analysis

Current Market Landscape

• Pyruvate Kinase Deficiency Market

PKD is an ultra-rare disease with an estimated prevalence of 3-4 per million globally. Currently, treatment options are limited primarily to supportive care, including transfusions and splenectomy, lacking targeted pharmacotherapy.

• Sickle Cell Disease and Hemolytic Anemias

The SCD market represents a multibillion-dollar sector, with an increasing demand for disease-modifying therapies. Existing treatments, such as hydroxyurea and newer agents like voxelotor, focus on symptom control and hemoglobin modulation but do not directly address metabolic deficiencies like those targeted by mitapivat sulfate.

Market Drivers

• Unmet Medical Need: Both PKD and SCD lack approved targeted therapies specifically modifying disease pathology, positioning mitapivat sulfate favorably upon regulatory approval.

• Potential for Orphan Drug Designation: As an orphan drug in PKD, mitapivat sulfate could benefit from market exclusivity, tax incentives, and accelerated approvals.

• Growing Diagnosis Rates: Advances in genetic testing increase diagnosis rates, expanding the patient pool for targeted therapies.

Competitive Landscape

Currently, few disease-specific agents are in late-stage development. Notable competitors include voxelotor (Oxbryta, GBT) and crizanlizumab (Novartis), primarily targeting symptomatology rather than metabolic correction.

Market Projections

• PKD Market Size: Expected to reach USD 500-700 million globally by 2030, considering the rare disease market growth and pipeline progression.

• SCD Market Expansion: The global SCD therapeutics market could approach USD 5 billion by 2028, driven by increased drug approvals and expanded indications.

• Revenue Potential for Mitapivat Sulfate: Assuming successful Phase III results and regulatory approval, peak sales could surpass USD 1 billion annually in primary markets (U.S., Europe, Japan), contingent on pricing, reimbursement, and adoption rates.

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Market Entry Strategy & Challenges

• Pricing & Reimbursement: As a rare disease therapy, mitapivat sulfate could command high pricing, especially with orphan drug status. Negotiating reimbursement will require demonstrating clear clinical benefit over existing supportive care.

• Market Penetration: Early engagement with patient advocacy groups and clinicians will facilitate uptake. Education on the metabolic mode of action could distinguish mitapivat from symptomatic treatments.

• Regulatory Hurdles: Accelerated pathways offer a viable route; however, confirming long-term safety and durable efficacy remains critical.

Future Outlook and Projections

With promising clinical outcomes, regulatory approvals are plausible within the next 2-3 years. Post-approval, a staged rollout targeting PKD first, followed by broader indications, would optimize market capture.

By 2030, mitapivat sulfate is poised to be a transformative therapy in hemolytic disorders, with a potential to generate significant revenues and to shape treatment paradigms for rare hematological diseases.

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Key Takeaways

• Clinical Progress: Mitapivat sulfate has demonstrated promising efficacy in PKD and SCD, with ongoing Phase III trials poised to establish its role as a disease-modifying agent.

• Market Opportunity: The rare disease nature of PKD offers high-value potential, complemented by an expanding SCD market driven by unmet needs and pipeline growth.

• Strategic Outlook: Early regulatory engagement, expanding indications, and robust clinical data will be critical for commercial success.

• Challenges & Considerations: Ensuring long-term safety, securing reimbursement, and educating clinicians are vital to market penetration.

• Long-term Impact: Mitapivat sulfate could redefine treatment approaches for hemolytic anemias by addressing underlying metabolic deficiencies rather than solely managing symptoms.

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FAQs

Q1: What is the primary mechanism of action of mitapivat sulfate?
A: It activates pyruvate kinase-R (PKR), boosting glycolytic activity in red blood cells, thereby improving RBC energy stability and reducing hemolysis.

Q2: Are there any approved treatments for pyruvate kinase deficiency?
A: Currently, no targeted approved therapies exist; management is supportive, making mitapivat sulfate's development significant.

Q3: When are regulatory decisions expected for mitapivat sulfate in major markets?
A: Regulatory submissions are anticipated following positive Phase III trial outcomes, with approvals possibly within 1-2 years thereafter.

Q4: How does mitapivat sulfate compare to existing SCD treatments?
A: Unlike symptom-focused agents, mitapivat sulfate targets a metabolic defect, offering the potential for disease modification.

Q5: What are the key challenges for market success?
A: Demonstrating long-term safety, attaining regulatory approval, securing reimbursement, and educating healthcare providers are essential challenges.

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References

1. [Clinical trial data and safety profile reports from Agios Pharmaceuticals]
2. [Results from the ACTIVATE trial indicating hemoglobin improvements]
3. [Regulatory and development updates from Agios Pharmaceuticals]