Givosiran

Givosiran
Names
Trade namesGivlaari
IUPAC name
  • N-[1,3-bis[3-[3-[5-[(2R,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]-2-[[3-[3-[5-[(2R,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]methyl]propan-2-yl]-12-[(2R,4R)-4-hydroxy-2-methylpyrrolidin-1-yl]-12-oxododecanamide
Clinical data
Drug classSmall interfering RNA (siRNA)[1]
Main usesHepatic porphyria[1]
Side effectsPain at the site of injection, nausea, tiredness[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • US: N (Not classified yet)
    Routes of
    use    		Subcutaneous injection
    Typical dose2.5 mg/kg q 1 month[2]
    External links
    AHFS/Drugs.comMonograph
    Legal
    License data
    Legal status
    Chemical and physical data
    FormulaC524H694F16N173O316P43S6
    Molar mass16300.42 g·mol−1
    3D model (JSmol)
    SMILES
    • C[C@@H]1C[C@H](CN1C(=O)CCCCCCCCCCC(=O)NC(COCCC(=O)NCCCNC(=O)CCCCO[C@H]2[C@@H]([C@H]([C@H]([C@H](O2)CO)O)O)NC(=O)C)(COCCC(=O)NCCCNC(=O)CCCCO[C@H]3[C@@H]([C@H]([C@H]([C@H](O3)CO)O)O)NC(=O)C)COCCC(=O)NCCCNC(=O)CCCCO[C@H]4[C@@H]([C@H]([C@H]([C@H](O4)CO)O)O)NC(=O)C)O
    InChI
    • InChI=1S/C78H139N11O30/c1-50-42-54(96)43-89(50)65(104)26-12-10-8-6-5-7-9-11-25-64(103)88-78(47-111-39-27-61(100)82-33-19-30-79-58(97)22-13-16-36-114-75-66(85-51(2)93)72(108)69(105)55(44-90)117-75,48-112-40-28-62(101)83-34-20-31-80-59(98)23-14-17-37-115-76-67(86-52(3)94)73(109)70(106)56(45-91)118-76)49-113-41-29-63(102)84-35-21-32-81-60(99)24-15-18-38-116-77-68(87-53(4)95)74(110)71(107)57(46-92)119-77/h50,54-57,66-77,90-92,96,105-110H,5-49H2,1-4H3,(H,79,97)(H,80,98)(H,81,99)(H,82,100)(H,83,101)(H,84,102)(H,85,93)(H,86,94)(H,87,95)(H,88,103)/t50-,54-,55-,56-,57-,66-,67-,68-,69+,70+,71+,72-,73-,74-,75-,76-,77-/m1/s1
    • Key:RUPXJRIDSUCQAN-PQNNUJSWSA-N

    Givosiran, sold under the brand name Givlaari, is a medication used to treat acute hepatic porphyria (AHP).[1] It is given by injection under the skin.[1] It is used in people over the age of 11.[1]

    Common side effects include pain at the site of injection, nausea, and tiredness.[1] Other side effects may include anaphylaxis, kidney problems, and liver problems.[2] It is a small interfering RNA (siRNA) that decreases the amount of the enzyme aminolevulinic acid synthase 1 (ALAS1) and therefore decreases the production of heme.[1][3]

    Givosiran was approved for medical use in the United States in 2019 and Europe in 2020.[2][1] In the United Kingdom a 189 mg vial costs the NHS about £4200 as of 2021.[3] This amount in the United States costs about 40,700 USD.[4]

    Medical uses

    Dosage

    It is generally given at a dose of 2.5 mg/kg.[2]

    History

    In November 2019, givosiran was approved in the United States for the treatment of adults with acute hepatic porphyria (AHP).[5][6]

    The U.S. Food and Drug Administration (FDA) granted the application for givosiran breakthrough therapy designation, priority review designation, and orphan drug designation.[5] The FDA granted the approval of Givlaari to Alnylam Pharmaceuticals.[5] The FDA considers it to be a first-in-class medication.[7]

    References

    1. 1 2 3 4 5 6 7 8 9 "Givlaari". Archived from the original on 12 November 2021. Retrieved 3 December 2021.
    2. 1 2 3 4 "Givosiran Monograph for Professionals". Drugs.com. Archived from the original on 26 October 2021. Retrieved 3 December 2021.
    3. 1 2 "Givosiran". SPS - Specialist Pharmacy Service. 18 June 2018. Archived from the original on 31 July 2020. Retrieved 3 December 2021.
    4. ↑ "Givlaari Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 22 January 2021. Retrieved 3 December 2021.
    5. 1 2 3 "FDA approves first treatment for inherited rare disease". U.S. Food and Drug Administration (FDA) (Press release). 20 November 2019. Archived from the original on 21 November 2019. Retrieved 20 November 2019. Public Domain This article incorporates text from this source, which is in the public domain.
    6. ↑ "Drug Trials Snapshots: Givlaari". U.S. Food and Drug Administration (FDA). 20 November 2019. Archived from the original on 24 January 2020. Retrieved 24 January 2020. Public Domain This article incorporates text from this source, which is in the public domain.
    7. ↑ "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Archived from the original on 16 September 2020. Retrieved 15 September 2020.
    Identifiers:
    • "Givosiran". Drug Information Portal. U.S. National Library of Medicine (NLM). Archived from the original on 29 November 2020. Retrieved 22 October 2021.
    This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.