Mitapivat

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Mitapivat
Mitapivat skeletal.svg
Clinical data
Trade names Pyrukynd
Other namesAG-348, Mitapivat sulfate (USAN US)
License data
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C24H26N4O3S
Molar mass 450.56 g·mol−1
3D model (JSmol)
  • O=C(N1CCN(CC2CC2)CC1)C1=CC=C(NS(=O)(=O)C2=CC=CC3=C2N=CC=C3)C=C1
  • 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, is a medication used to treat hemolytic anemia. [1] It is taken as the sulfate hydrate salt by mouth. [1] Mitapivat is a pyruvate kinase activator. [1]

Contents

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. [2] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. [6] [7]

Medical uses

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

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. [8] 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. [8] [9]

History

The FDA 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

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. [10] The applicant for this medicinal product is Agios Netherlands B.V. [10] Mitapivat was approved for medical use in the European Union in November 2022. [2] [11]

Names

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

Related Research Articles

<span class="mw-page-title-main">Hemolytic anemia</span> Reduced oxygen-carrying ability of the blood due to breakdown of red blood cells

Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels or elsewhere in the human body (extravascular). This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically. Hemolytic anemia accounts for 5% of all existing anemias. It has numerous possible consequences, ranging from general symptoms to life-threatening systemic effects. The general classification of hemolytic anemia is either intrinsic or extrinsic. Treatment depends on the type and cause of the hemolytic anemia.

<span class="mw-page-title-main">Pyruvate kinase deficiency</span> Medical condition

Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive. Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.

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References

  1. 1 2 3 4 5 6 "Pyrukynd- mitapivat tablet, film coated Pyrukynd- mitapivat kit". DailyMed. 23 February 2022. Archived from the original on 3 March 2022. Retrieved 3 March 2022.
  2. 1 2 3 "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.
  3. 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.PD-icon.svg 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. 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.
  6. ↑ "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". U.S. Food and Drug Administration (FDA). 10 January 2023. Retrieved 22 January 2023.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. ↑ New Drug Therapy Approvals 2022 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 14 January 2024. Retrieved 14 January 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  8. 1 2 "Mitapivat (Code C157039)". NCI Thesaurus. 31 January 2022. Archived from the original on 20 February 2022. Retrieved 19 February 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. ↑ "PK-R allosteric activator AG-348". NCI Drug Dictionary. National Cancer Institute. Archived from the original on 10 August 2019. Retrieved 19 February 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  10. 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.
  11. ↑ "Pyrukynd Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  12. ↑ World Health Organization (2017). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 78". WHO Drug Information. 31 (3): 539. hdl: 10665/330961 .

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