Chemistry:Mitapivat

From HandWiki

Mitapivat, sold under the brand name Pyrukynd among others, is a medication used to treat different types of anemia.[1][2] It is taken as the sulfate hydrate salt by mouth.[1] Mitapivat is a pyruvate kinase activator.[1][2]

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.[3]

Mitapivat was approved for medical use in the United States in February 2022,[1][3][4][5] and in the European Union in November 2022.[6] The US Food and Drug Administration considers it to be a first-in-class medication.[7][8]

Medical uses

Mitapivat is indicated for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency.[1][5]

In December 2025, mitapivat (brand name Aqvesme) was approved in the US for the treatement of anemia in adults with alpha- or beta-thalassemia.[2][9]

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.[10] 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.[10][11]

History

The US Food and Drug Administration approved mitapivat based on evidence from two clinical trials of 107 participants with pyruvate kinase deficiency.[3] 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.[3] 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.[3] 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.[3] In Trial 2, all participants received mitapivat for an average duration of about 40 weeks.[3] Trial 2 was conducted at 17 sites in the following countries: Canada, Denmark, France, Ireland, Italy, Netherlands, Thailand, United Kingdom, and the United States.[3]

Society and culture

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.[12] The applicant for this medicinal product is Agios Netherlands B.V.[12] Mitapivat was approved for medical use in the European Union in November 2022.[6][13]

Names

Mitapivat is the international nonproprietary name (INN).[14]

Mitapivat is sold under the brand names Pyrukynd[1][6] and Aqvesme.[2]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Cite error: Invalid <ref> tag; no text was provided for refs named Pyrukynd FDA label
  2. ↑ 2.0 2.1 2.2 2.3 Cite error: Invalid <ref> tag; no text was provided for refs named Aqvesme FDA label
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "Drug Trials Snapshot: Pyrukynd". 1 June 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-pyrukynd.  Public Domain This article incorporates text from this source, which is in the public domain.
  4. ↑ "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.
  5. ↑ 5.0 5.1 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.
  6. ↑ 6.0 6.1 6.2 "Pyrukynd EPAR". 14 September 2022. https://www.ema.europa.eu/en/medicines/human/EPAR/pyrukynd.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. ↑ "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". 10 January 2023. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2022.  Public Domain This article incorporates text from this source, which is in the public domain.
  8. ↑ (PDF) New Drug Therapy Approvals 2022 (Report). January 2024. https://www.fda.gov/media/164429/download. Retrieved 14 January 2024.  Public Domain 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. https://www.globenewswire.com/news-release/2025/12/24/3210205/0/en/U-S-FDA-Approves-Agios-AQVESME-mitapivat-for-the-Treatment-of-Anemia-in-Adults-with-Alpha-or-Beta-Thalassemia.html. 
  10. ↑ 10.0 10.1 "Mitapivat (Code C157039)". 31 January 2022. https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C157039.  Public Domain This article incorporates text from this source, which is in the public domain.
  11. ↑ "PK-R allosteric activator AG-348". NCI Drug Dictionary. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-drug.  Public Domain This article incorporates text from this source, which is in the public domain.
  12. ↑ 12.0 12.1 "Pyrukynd: Pending EC decision". 15 September 2022. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/pyrukynd.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  13. ↑ "Pyrukynd Product information". https://ec.europa.eu/health/documents/community-register/html/h1662.htm. 
  14. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 78". WHO Drug Information 31 (3): 539. 2017. 

Further reading

  • 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



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Mitapivat&oldid=4242911"