Sevabertinib is a small-molecule, orally active kinase inhibitor developed as BAY-2927088. It is a mutant-selective dual inhibitor of HER2 (ERBB2) and EGFR, with activity against activating HER2 mutations including tyrosine kinase domain alterations. FDA approved sevabertinib in November 2025 under the trade name HYRNUO for a defined population of adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors contain HER2 tyrosine kinase domain activating mutations and who have received prior systemic therapy.
Sevabertinib is identified by FDA GSRS as a chemical substance with absolute stereochemistry and one defined stereocenter. The FDA active-moiety record gives the molecular formula C24H25ClN4O5 and molecular weight 484.93 g/mol. The FDA record also identifies a separate sevabertinib hydrate substance, reflecting the solid-state form used in the marketed product.
Key identity information:
The systematic chemical name of sevabertinib is 3-(3-chloro-2-methoxyanilino)-2-[3-[[(2S)-1,4-dioxan-2-yl]methoxy]-4-pyridinyl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one. FDA's approved labeling describes the drug substance as the hydrate and specifies that the strength of HYRNUO is based on the anhydrous form.
The marketed drug substance is particularly notable for its hydration behavior. FDA describes it as a non-stoichiometric hydrate, while the Japanese accepted-name database likewise describes sevabertinib hydrate as C24H25ClN4O5·xH2O.
Sevabertinib is a reversible kinase inhibitor of HER2 and also exhibits activity against EGFR. In vitro studies demonstrated inhibition of HER2 phosphorylation and downstream signaling in cancer cells carrying HER2 alterations. It also inhibits proliferation of cells expressing altered or amplified HER2.
Unlike irreversible EGFR inhibitors, sevabertinib is characterized as a reversible dual EGFR-HER2 inhibitor with selectivity relative to wild-type EGFR.
The current FDA-approved application is the treatment of adult patients with locally advanced or metastatic non-squamous NSCLC whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test, following prior systemic therapy. The indication was granted accelerated approval based on objective response rate and duration of response.
The recommended FDA dosage of HYRNUO is 20 mg orally twice daily with food, and the approved tablet strength is 10 mg.
As a synthetic small-molecule API, sevabertinib requires conventional pharmaceutical analytical testing combined with specific control of its hydrate state.
A suitable quality-control program may include:
Because FDA identifies sevabertinib as a non-stoichiometric hydrate, water content and solid-state form are particularly important characteristics for API control.
Sevabertinib is manufactured as a chemically synthesized small molecule. Production requires controlled reaction conditions, purification, solvent removal, crystallization and solid-state control to obtain material meeting the applicable pharmaceutical specification.
The hydrate state must be controlled during isolation, drying, packaging and storage because the drug substance is described as a non-stoichiometric hydrate.
FDA describes sevabertinib as a white to off-white to yellow to pinkish powder in its non-stoichiometric hydrate form. It is slightly soluble in aqueous solution at pH 2 and practically insoluble in aqueous solutions at pH 4.5 and above.
The anhydrous active moiety has a molecular weight of 484.93 g/mol, whereas the hydrate has an approximate one-water formula of C24H27ClN4O6 and calculated molecular weight 502.9 g/mol in the PubChem record. However, because FDA specifically describes the pharmaceutical substance as a non-stoichiometric hydrate, the one-water value should not be treated as the universal API molecular weight.
The approved HYRNUO tablets are stored at 20°C to 25°C, with permitted excursions between 15°C and 30°C. The finished product is supplied as 10 mg film-coated tablets.
For bulk API, storage should follow the validated drug-substance stability specification, particularly because hydration state can be relevant to the physical form of sevabertinib.
A commercial Sevabertinib API documentation package may include:
Sevabertinib is a specialized oncology API requiring control of both chemical purity and solid-state/hydration characteristics. Consistent synthetic processing, validated chromatographic analysis, residual-solvent control, water determination and appropriate solid-state characterization are important for reproducible pharmaceutical-grade material.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |