Sevabertinib

Sevabertinib
Clinical data
Trade namesHyrnuo
Other namesBAY2927088, sevabertinib hydrate (JAN JP)
AHFS/Drugs.comhyrnuo
License data
Routes of
administration		By mouth
Drug classAntineoplastic
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC24H25ClN4O5
Molar mass484.94 g·mol−1
3D model (JSmol)
  • COC1=C(C=CC=C1Cl)NC2=C(NC3=C2C(=O)NCC3)C4=C(C=NC=C4)OC[C@@H]5COCCO5
  • InChI=1S/C24H25ClN4O5/c1-31-23-16(25)3-2-4-18(23)29-22-20-17(6-8-27-24(20)30)28-21(22)15-5-7-26-11-19(15)34-13-14-12-32-9-10-33-14/h2-5,7,11,14,28-29H,6,8-10,12-13H2,1H3,(H,27,30)/t14-/m0/s1
  • Key:VYQVHWNNPKOJEA-AWEZNQCLSA-N

Sevabertinib, sold under the brand name Hyrnuo, is an anti-cancer medication used for the treatment of non-small cell lung cancer.[1] Sevabertinib is a kinase inhibitor.[1] It is taken by mouth.[1]

Sevabertinib was approved for medical use in the United States in November 2025.[2]

Medical uses

Sevabertinib is indicated for the treatment of adults with locally advanced or metastatic non-squamous non-small cell lung cancer whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations.[1][2]

Adverse effects

The US prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease/pneumonitis, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity.[2]

History

Efficacy was evaluated in people with unresectable or metastatic, non-squamous non-small cell lung cancer with HER2 (ERBB2) tyrosine kinase domain activating mutations who had received prior systemic therapy and received sevabertinib in SOHO-01 (NCT05099172), an open-label, single-arm, multi-center, multi-cohort clinical trial.[2] HER2 (ERBB2) activating mutations were determined in tumor tissue or plasma by local laboratories prior to enrollment.[2]

The US Food and Drug Administration granted the application for sevabertinib priority review, breakthrough therapy, and orphan drug designations.[2]

Synthesis

The original route of synthesis of sevabertinib was disclosed in a patent filed by Bayer[3]. The route is shown below:

The route is convergent. The first structural fragment (Intermediate 2-1) is synthesized by the nucleophilic aromatic substitution of the nitrile and 1,4-dioxane-2-methanol in a basic condition, followed by hydrogenation catalyzed by Raney nickel. The synthesis of the other structural fragment (Intermediate 5-1) starts from a reaction of the amine with thiophosgene to form the isothiocyanate, followed by a condensation reaction with the protected β-carbonyl lactam and an acidic deprotection. The two intermediates go through further condensations to give racemic sevabertinib, which finally goes through a chiral resolution by preparative chiral HPLC to give the desired enantiomer.

Alternatively, to save the chiral resolution in the end, sevabertinib can also be synthesized from a chiral starting material (2R)-1,4-dioxane-2-methanol in a likewise manner.

Society and culture

Sevabertinib was approved for medical use in the United States in November 2025.[4][5]

Names

Sevabertinib is the international nonproprietary name.[6]

Sevabertinib is sold under the brand name Hyrnuo.[1][4]

References

  1. ^ a b c d e f "Hyrnuo- sevabertinib tablet, film coated". DailyMed. 3 December 2025. Retrieved 28 December 2025.
  2. ^ a b c d e f "FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer". U.S. Food and Drug Administration (FDA). 19 November 2025. Retrieved 21 November 2025. This article incorporates text from this source, which is in the public domain.
  3. ^ (US20250136599A1, "4H-pyrrolo[3,2-c]pyridin-4-one compounds", published 1 May 2025 )
  4. ^ a b "U.S. FDA Approves Hyrnuo (sevabertinib) for Previously Treated Patients with HER2-Mutated Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer" (Press release). Bayer. 20 November 2025. Retrieved 21 November 2025 – via Business Wire.
  5. ^ "U.S. FDA grants accelerated approval to Bayer's Hyrnuo (sevabertinib) for patients with previously treated advanced HER2-mutant non-small cell lung cancer". Bayer (Press release). 20 November 2025. Retrieved 21 November 2025.
  6. ^ World Health Organization (2025). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 93". WHO Drug Information. 39 (1). hdl:10665/381075.

Further reading

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