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]

## Contents

* 1 Medical uses
* 2 Adverse effects
* 3 History
* 4 Synthesis
* 5 Society and culture
* 5.1 Legal status
* 5.2 Names
* 6 References
* 7 Further reading
* 8 External links

## 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

### Legal status

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. 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

* "Sevabertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer". The New England Journal of Medicine 393 (18): 1819–1832. November 2025. doi:10.1056/NEJMoa2511065. PMID 41104928.
* "Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer". Cancer Discovery: OF1–OF14. October 2025. doi:10.1158/2159-8290.CD-25-0605. PMID 41090369.

## External links

* "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

* v
* t
* e

Targeted cancer therapy / antineoplastic agents (L01)

CI monoclonal antibodies ("-mab")|

| Receptor tyrosine kinase|

* ErbB: HER1/EGFR (Cetuximab
* Panitumumab)
* HER2/neu (Trastuzumab
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|

Others for solid tumors|

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RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK). c-MET inhibitor: Cabozantinib (also VEGFR2).

|

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