Mitapivat

Mitapivat
Clinical data
Trade names	Pyrukynd, Aqvesme
Other names	AG-348, Mitapivat sulfate (USAN US)
AHFS/Drugs.com	Monograph
MedlinePlus	a622018
License data	US DailyMed: Mitapivat;
Routes of; administration	By mouth
Drug class	Pyruvate kinase activator
ATC code	B06AX04 (WHO) ;
Legal status
Legal status	US: ℞-only; EU: Rx-only;
Identifiers
CAS Number	1260075-17-9;
PubChem CID	59634741;
IUPHAR/BPS	10473;
DrugBank	DB16236; as salt: DBSALT003215;
ChemSpider	29763395;
UNII	2WTV10SIKH; as salt: N4JTA67V3O;
KEGG	as salt: D11408;
ChEMBL	ChEMBL4299940; as salt: ChEMBL4297223;
Chemical and physical data
Formula	C24H26N4O3S
Molar mass	450.56 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(N1CCN(CC2CC2)CC1)C1=CC=C(NS(=O)(=O)C2=CC=CC3=C2N=CC=C3)C=C1;
	InChI InChI=1S/C24H26N4O3S/c29-24(28-15-13-27(14-16-28)17-18-6-7-18)20-8-10-21(11-9-20)26-32(30,31)22-5-1-3-19-4-2-12-25-23(19)22/h1-5,8-12,18,26H,6-7,13-17H2; Key:XAYGBKHKBBXDAK-UHFFFAOYSA-N;

Mitapivat, sold under the brand name Pyrukynd among others, is a medication used to treat different types of anemia. It is taken as the sulfate hydrate salt by mouth. Mitapivat is a pyruvate kinase activator.

The most common side effects include decreases in estrone and estradiol (types of the estrogen hormone) in men, increased urate (a type of salt in the body), back pain, and joint stiffness.

Mitapivat was approved for medical use in the United States in February 2022, and in the European Union in November 2022. The US Food and Drug Administration considers it to be a first-in-class medication.

Medical uses

Mitapivat is indicated for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency.

In December 2025, mitapivat (brand name Aqvesme) was approved in the US for the treatement of anemia in adults with alpha- or beta-thalassemia.

Mitapivat has also been evaluated for the treatment of sickle cell disease, with a promising phase 2 trial.

Pharmacology

Mechanism of action

Mitapivat binds to and activates pyruvate kinase, thereby enhancing glycolytic pathway activity, improving adenosine triphosphate (ATP) levels and reducing 2,3-diphosphoglycerate (2,3-DPG) levels. Mutations in pyruvate kinase cause deficiency in pyruvate kinase which prevents adequate red blood cell (RBC) glycolysis, leading to a buildup of the upstream glycolytic intermediate 2,3-DPG and deficiency in the pyruvate kinase product ATP.

History

The US Food and Drug Administration approved mitapivat based on evidence from two clinical trials of 107 participants with pyruvate kinase deficiency. Trial 1 (NCT03548220) of 80 adults with pyruvate kinase deficiency who did not receive regular blood transfusions and trial 2 (NCT03559699) of 27 adults with pyruvate kinase deficiency who received regular blood transfusions. In trial 1, participants were randomly assigned to receive either mitapivat or a matched placebo tablet for an average duration of about 24 weeks. Neither the participants nor the healthcare providers knew which treatment was being given during the trial. Trial 1 was conducted at 36 sites in the following countries: Brazil, Canada, Denmark, France, Germany, Italy, Japan, Republic of Korea, Netherlands, Spain, Switzerland, Turkey, United Kingdom, and the United States. In Trial 2, all participants received mitapivat for an average duration of about 40 weeks. Trial 2 was conducted at 17 sites in the following countries: Canada, Denmark, France, Ireland, Italy, Netherlands, Thailand, United Kingdom, and the United States.

Society and culture

Legal status

In September 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Pyrukynd, intended for the treatment of an inherited condition called pyruvate kinase deficiency. The applicant for this medicinal product is Agios Netherlands B.V. Mitapivat was approved for medical use in the European Union in November 2022.

Names

Mitapivat is the international nonproprietary name (INN).

Mitapivat is sold under the brand names Pyrukynd and Aqvesme.

References

1 2 3 4 5 6 7 "Pyrukynd- mitapivat tablet, film coated Pyrukynd- mitapivat kit". DailyMed. 23 February 2022. Archived from the original on 3 March 2022. Retrieved 3 March 2022.
1 2 3 4 5 "Highlights of prescribing information - AQVESMETM (mitapivat) tablets, for oral use" (PDF). www.accessdata.fda.gov.
1 2 3 4 "Pyrukynd EPAR". European Medicines Agency (EMA). 14 September 2022. Retrieved 5 December 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
1 2 3 4 5 6 7 8 "Drug Trials Snapshot: Pyrukynd". U.S. Food and Drug Administration (FDA). 1 June 2023. Retrieved 1 June 2023.^{[dead link]} This article incorporates text from this source, which is in the public domain.
↑ "Agios Announces FDA Approval of Pyrukynd (mitapivat) as First Disease-Modifying Therapy for Hemolytic Anemia in Adults with Pyruvate Kinase Deficiency" (Press release). Agios Pharmaceuticals. 17 February 2022. Archived from the original on 20 February 2022. Retrieved 19 February 2022 – via GlobeNewswire.
1 2 Gormley N. "Pyrukynd (mitapivat) tablets NDA approval" (PDF). Center for Drug Evaluation and Research. Letter to Christina Baladi (Agios Pharmaceuticals, Inc.). U.S. Food and Drug Administration. Archived from the original (PDF) on 20 February 2022.
↑ "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". U.S. Food and Drug Administration (FDA). 10 January 2023. Archived from the original on 10 January 2023. Retrieved 22 January 2023. This article incorporates text from this source, which is in the public domain.
↑ New Drug Therapy Approvals 2022. U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original (PDF) on 14 January 2024. Retrieved 14 January 2024. This article incorporates text from this source, which is in the public domain.
↑ "U.S. FDA Approves Agios' Aqvesme (mitapivat) for the Treatment of Anemia in Adults with Alpha- or Beta-Thalassemia". Agios Pharmaceuticals. 24 December 2025. Retrieved 30 December 2025 – via GlobeNewswire News Room.
↑ Idowu M, Otieno L, Dumitriu B, Lobo CL, Thein SL, Andemariam B, et al. (January 2025). "Safety and efficacy of mitapivat in sickle cell disease (RISE UP): results from the phase 2 portion of a global, double-blind, randomised, placebo-controlled trial". The Lancet. Haematology. 12 (1) e35–e44. doi:10.1016/S2352-3026(24)00319-3. PMID 39644907.
1 2 "Mitapivat (Code C157039)". NCI Thesaurus. 31 January 2022. Archived from the original on 20 February 2022. Retrieved 19 February 2022. This article incorporates text from this source, which is in the public domain.
↑ "PK-R allosteric activator AG-348". NCI Drug Dictionary. National Cancer Institute. Archived from the original on 10 August 2019. Retrieved 19 February 2022. This article incorporates text from this source, which is in the public domain.
1 2 "Pyrukynd: Pending EC decision". European Medicines Agency (EMA). 15 September 2022. Archived from the original on 19 September 2022. Retrieved 18 September 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
↑ "Pyrukynd Product information". Union Register of medicinal products. Retrieved 3 March 2023.
↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 78". WHO Drug Information. 31 (3): 539. 2017. hdl:10665/330961.

External links

Clinical trial number NCT03548220 for "A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)" at ClinicalTrials.gov
Clinical trial number NCT03559699 for "A Study Evaluating the Efficacy and Safety of AG-348 in Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)" at ClinicalTrials.gov
Clinical trial number NCT04770779 for "A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT) (ENERGIZE-T)" at ClinicalTrials.gov
Clinical trial number NCT04770753 for "A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)" at ClinicalTrials.gov

[Pyrukynd_FDA_label-1] 1 2 3 4 5 6 7 "Pyrukynd- mitapivat tablet, film coated Pyrukynd- mitapivat kit". DailyMed. 23 February 2022. Archived from the original on 3 March 2022. Retrieved 3 March 2022.

[Aqvesme_FDA_label-2] 1 2 3 4 5 "Highlights of prescribing information - AQVESMETM (mitapivat) tablets, for oral use" (PDF). www.accessdata.fda.gov.

[Pyrukynd_EPAR-3] 1 2 3 4 "Pyrukynd EPAR". European Medicines Agency (EMA). 14 September 2022. Retrieved 5 December 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

[Drug_Trials_Snapshot:_Pyrukynd-4] 1 2 3 4 5 6 7 8 "Drug Trials Snapshot: Pyrukynd". U.S. Food and Drug Administration (FDA). 1 June 2023. Retrieved 1 June 2023.^{[dead link]} This article incorporates text from this source, which is in the public domain.

[Agios_PR-5] "Agios Announces FDA Approval of Pyrukynd (mitapivat) as First Disease-Modifying Therapy for Hemolytic Anemia in Adults with Pyruvate Kinase Deficiency" (Press release). Agios Pharmaceuticals. 17 February 2022. Archived from the original on 20 February 2022. Retrieved 19 February 2022 – via GlobeNewswire.

[FDA_approval_letter-6] 1 2 Gormley N. "Pyrukynd (mitapivat) tablets NDA approval" (PDF). Center for Drug Evaluation and Research. Letter to Christina Baladi (Agios Pharmaceuticals, Inc.). U.S. Food and Drug Administration. Archived from the original (PDF) on 20 February 2022.

[New_Drug_Therapy_Approvals_2022-7] "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". U.S. Food and Drug Administration (FDA). 10 January 2023. Archived from the original on 10 January 2023. Retrieved 22 January 2023. This article incorporates text from this source, which is in the public domain.

[8] New Drug Therapy Approvals 2022. U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original (PDF) on 14 January 2024. Retrieved 14 January 2024. This article incorporates text from this source, which is in the public domain.

[9] "U.S. FDA Approves Agios' Aqvesme (mitapivat) for the Treatment of Anemia in Adults with Alpha- or Beta-Thalassemia". Agios Pharmaceuticals. 24 December 2025. Retrieved 30 December 2025 – via GlobeNewswire News Room.

[10] Idowu M, Otieno L, Dumitriu B, Lobo CL, Thein SL, Andemariam B, et al. (January 2025). "Safety and efficacy of mitapivat in sickle cell disease (RISE UP): results from the phase 2 portion of a global, double-blind, randomised, placebo-controlled trial". The Lancet. Haematology. 12 (1) e35–e44. doi:10.1016/S2352-3026(24)00319-3. PMID 39644907.

[NCI_C157039-11] 1 2 "Mitapivat (Code C157039)". NCI Thesaurus. 31 January 2022. Archived from the original on 20 February 2022. Retrieved 19 February 2022. This article incorporates text from this source, which is in the public domain.

[12] "PK-R allosteric activator AG-348". NCI Drug Dictionary. National Cancer Institute. Archived from the original on 10 August 2019. Retrieved 19 February 2022. This article incorporates text from this source, which is in the public domain.

[Pyrukynd:_Pending_EC_decision-13] 1 2 "Pyrukynd: Pending EC decision". European Medicines Agency (EMA). 15 September 2022. Archived from the original on 19 September 2022. Retrieved 18 September 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

[14] "Pyrukynd Product information". Union Register of medicinal products. Retrieved 3 March 2023.

[WHORecList78-15] "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 78". WHO Drug Information. 31 (3): 539. 2017. hdl:10665/330961.