Chemistry:Sevabertinib

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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 original route of synthesis of Sevabertinib

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. ↑ 1.0 1.1 1.2 1.3 1.4 Cite error: Invalid <ref> tag; no text was provided for refs named Hyrnuo FDA label
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer". 19 November 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-non-squamous-non-small-cell-lung-cancer.  Public Domain This article incorporates text from this source, which is in the public domain.
  3. ↑ ("4H-pyrrolo[3,2-c]pyridin-4-one compounds" patent US20250136599A1, published 2025-05-01)
  4. ↑ 4.0 4.1 "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. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 93". WHO Drug Information 39 (1). 2025. 

Further reading



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