Sebetralstat is a novel, orally active small-molecule plasma kallikrein inhibitor developed for the on-demand treatment of acute attacks of hereditary angioedema (HAE). It is also known by its development code KVD900/KVD-900. The compound has CAS Number 1933514-13-6, molecular formula C₂₆H₂₆FN₅O₄, and molecular weight 491.52 g/mol. These chemical identity details are confirmed by the U.S. FDA Global Substance Registration System and FDA's review of the approved drug application.
Sebetralstat works by selectively inhibiting plasma kallikrein, an important component of the kallikrein-kinin pathway. Excessive bradykinin generation is a key mechanism involved in the swelling attacks associated with hereditary angioedema. By inhibiting plasma kallikrein, sebetralstat reduces kallikrein activity and consequently helps reduce the downstream generation of bradykinin responsible for HAE symptoms.
The FDA approved sebetralstat under the brand EKTERLY in July 2025 for the treatment of acute attacks of hereditary angioedema in adults and pediatric patients aged 12 years and older. The approval represents an important development in HAE treatment because sebetralstat provides an orally administered on-demand option rather than requiring administration by injection.
From an API perspective, sebetralstat is a chemically defined small molecule rather than a peptide or biologic. FDA describes the drug substance as a white to off-white crystalline powder with poor aqueous solubility. Its solubility increases under lower-pH conditions, while the approved product labeling describes the substance as slightly soluble in ethanol, acetone and isopropanol and practically insoluble in water.
The chemical structure contains a substituted pyridine, pyrazole-carboxamide and pyridone-containing framework, with fluorine, nitrogen and oxygen heteroatoms. The official chemical name is N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxo-1,2-dihydropyridin-1-yl)methyl]phenyl}methyl)-1H-pyrazole-4-carboxamide.
For pharmaceutical API manufacturing, the quality profile of sebetralstat requires appropriate control of assay, organic impurities, degradation products, residual solvents and elemental impurities. FDA's Chemistry review states that the submitted drug-substance specification was designed in accordance with relevant ICH Q3A, Q3C, Q3D and Q6A principles, with validated analytical methods used to demonstrate the quality of the drug substance.
Because sebetralstat is a relatively recent pharmaceutical substance, it is important not to assign generic numerical API limits without authoritative support. FDA's public chemistry review confirms that a detailed drug-substance specification exists, but several acceptance criteria are redacted in the publicly available review. Therefore, numerical values such as assay limits, individual impurity limits, total impurities, loss on drying and residue on ignition should be taken from the applicable approved or customer-specific API specification rather than presented as universal pharmacopoeial limits.
Sebetralstat is supplied in the approved product as a 300 mg immediate-release film-coated tablet. The FDA-approved product contains sebetralstat as the active ingredient, while the finished formulation includes excipients such as microcrystalline cellulose, croscarmellose sodium, povidone, magnesium stearate and coating components. These finished-product details should not be confused with the API specification.
The development of sebetralstat represents an important advance in rare-disease pharmaceutical research and targeted treatment of HAE. Its oral administration, selective plasma kallikrein mechanism and regulatory approval make it a significant specialty pharmaceutical API for research, development and commercial manufacturing programs.
For API manufacturers and pharmaceutical companies, sebetralstat requires a quality-focused manufacturing approach incorporating validated analytical methods, impurity characterization, residual-solvent control, elemental-impurity assessment, stability studies and appropriate packaging. FDA's review confirms that the drug substance manufacturing process and analytical control strategy were evaluated for the approved application.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |