Mitapivat Explained

Usan:Mitapivat sulfate
Tradename:Pyrukynd
Dailymedid:Mitapivat
Routes Of Administration:By mouth
Atc Prefix:B06
Atc Suffix:AX04
Legal Us:Rx-only
Legal Us Comment:[1]
Legal Eu:Rx-only
Index2 Label:as salt
Cas Number:1260075-17-9
Pubchem:59634741
Iuphar Ligand:10473
Drugbank:DB16236
Drugbank2:DBSALT003215
Chemspiderid:29763395
Unii:2WTV10SIKH
Unii2:N4JTA67V3O
Kegg2:D11408
Chembl:4299940
Chembl2:4297223
Synonyms:AG-348
C:24
H:26
N:4
O:3
S:1
Smiles:O=C(N1CCN(CC2CC2)CC1)C1=CC=C(NS(=O)(=O)C2=CC=CC3=C2N=CC=C3)C=C1
Stdinchi: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
Stdinchikey:XAYGBKHKBBXDAK-UHFFFAOYSA-N

Mitapivat, sold under the brand name Pyrukynd, is a medication used to treat hemolytic 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,[2] [3] [4] and in the European Union in November 2022. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[5] [6]

Medical uses

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

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.[7] [8]

History

The FDA 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

On 15 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.[9] Mitapivat was approved for medical use in the European Union in November 2022.[10] [11]

Names

Mitapivat is the international nonproprietary name (INN).[12]

Further reading

External links

Notes and References

  1. Web site: Pyrukynd- mitapivat tablet, film coated Pyrukynd- mitapivat kit . DailyMed . 23 February 2022 . 3 March 2022 . 3 March 2022 . https://web.archive.org/web/20220303154400/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4ccee896-e313-4c6c-9674-b4746ada0a90 . live .
  2. Web site: Drug Trials Snapshot: Pyrukynd . U.S. Food and Drug Administration (FDA) . 1 June 2023 . 1 June 2023.
  3. Agios Announces FDA Approval of Pyrukynd (mitapivat) as First Disease-Modifying Therapy for Hemolytic Anemia in Adults with Pyruvate Kinase Deficiency . Agios Pharmaceuticals . GlobeNewswire . 17 February 2022 . 19 February 2022 . 20 February 2022 . https://web.archive.org/web/20220220000640/https://www.globenewswire.com/news-release/2022/02/17/2387542/31990/en/Agios-Announces-FDA-Approval-of-PYRUKYND-mitapivat-as-First-Disease-Modifying-Therapy-for-Hemolytic-Anemia-in-Adults-with-Pyruvate-Kinase-Deficiency.html . live .
  4. Gormley N . Center for Drug Evaluation and Research . U.S. Food and Drug Administration . Pyrukynd (mitapivat) tablets NDA approval . Christina Baladi (Agios Pharmaceuticals, Inc.) . https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/216196Orig1s000ltr.pdf .
  5. Web site: Advancing Health Through Innovation: New Drug Therapy Approvals 2022 . U.S. Food and Drug Administration (FDA) . 10 January 2023 . 22 January 2023.
  6. New Drug Therapy Approvals 2022 . U.S. Food and Drug Administration (FDA) . January 2024 . PDF . 14 January 2024 . https://web.archive.org/web/20240114065648/https://www.fda.gov/media/164429/download . 14 January 2024 . live .
  7. Web site: Mitapivat (Code C157039) . NCI Thesaurus . 31 January 2022 . 19 February 2022 . 20 February 2022 . https://web.archive.org/web/20220220004448/https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C157039 . live .
  8. Web site: PK-R allosteric activator AG-348 . NCI Drug Dictionary . National Cancer Institute . 19 February 2022 . 10 August 2019 . https://web.archive.org/web/20190810012312/https://www.cancer.gov/publications/dictionaries/cancer-drug . live .
  9. Web site: Pyrukynd: Pending EC decision . European Medicines Agency (EMA) . 15 September 2022 . 18 September 2022 . 19 September 2022 . https://web.archive.org/web/20220919055217/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/pyrukynd . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  10. Web site: Pyrukynd EPAR . European Medicines Agency (EMA) . 14 September 2022 . 5 December 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  11. Web site: Pyrukynd Product information . Union Register of medicinal products . 3 March 2023.
  12. ((World Health Organization)) . International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 78 . WHO Drug Information . 31 . 3 . 2017 . 10665/330961 . free . World Health Organization . 539 .

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