Sevabertinib

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]

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]

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]

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]

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.

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

Sevabertinib is the international nonproprietary name.^[6]

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

• "Sevabertinib". https://www.cancer.gov/publications/dictionaries/cancer-drug/def/sevabertinib. 
• "Sevabertinib ( Code - C185187 )". https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C185187. 
• Clinical trial number NCT05099172 for "First in Human Study of BAY2927088 in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations in the Genes of Epidermal Growth Factor Receptor (EGFR) and/or Human Epidermal Growth Factor Receptor 2 (HER2)" at ClinicalTrials.gov

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