Sebetralstat

Sebetralstat is an oral on-demand therapy to treat acute hereditary angioedema (HAE) attacks. It is designed to reduce the severity and duration of HAE attacks by inhibiting plasma kallikrein, an enzyme that plays a key role in swelling during HAE attacks. Sebetralstat is marketed under the brand name EKTERLY and was approved by the U.S. Food and Drug Administration (FDA) in July 2025 for use in adults and children aged 12 years of age and older. It represents the first orally administered treatment option for acute HAE attacks.^[1][2]

Sebetralstat

Clinical data
Trade names	EKTERLY
Other names	KVD-900, KVD900, Sebetralstat
AHFS/Drugs.com	Ekterly
License data	US DailyMed: Sebetralstat
Routes of administration	By mouth, Oral
ATC code	B06AC08 (WHO)
Legal status
Legal status	AU: TBD US: ℞-only EU: TBD ℞ (Prescription only)
Identifiers
IUPAC name N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-[[4-[(2-oxopyridin-1-yl)methyl]phenyl]methyl]pyrazole-4-carboxamide
CAS Number	1933514-13-6
PubChem CID	121365142
IUPHAR/BPS	11947
DrugBank	DB18305
ChemSpider	115006749
UNII	O5ZD2TU2B7
KEGG	D12396
ChEMBL	ChEMBL5095248
Chemical and physical data
Formula	C26H26FN5O4
Molar mass	491.523 g·mol−1
3D model (JSmol)	Interactive image
SMILES COCC1=NN(C=C1C(=O)NCC2=NC=CC(=C2F)OC)CC3=CC=C(C=C3)CN4C=CC=CC4=O
InChI InChI=1S/C26H26FN5O4/c1-35-17-22-20(26(34)29-13-21-25(27)23(36-2)10-11-28-21)16-32(30-22)15-19-8-6-18(7-9-19)14-31-12-4-3-5-24(31)33/h3-12,16H,13-15,17H2,1-2H3,(H,29,34) Key:KGMPDQIYDKKXRD-UHFFFAOYSA-N

Mechanism of action

Sebetralstat is a competitive, reversible inhibitor of plasma kallikrein. Plasma kallikrein is a serine protease that cleaves high molecular weight kininogen (HK), releasing bradykinin (BK), which increases vascular permeability through activation of BK receptors, causing edema. Sebetralstat inhibits the cleavage of HK to BK, preventing activation of the BK receptors and halting the progression of HAE attacks. Sebetralstat also inhibits the positive feedback mechanism of the kallikrein kinin system by plasma kallikrein, thereby reducing factor XIIa and additional plasma kallikrein generation.^[1]

Sebetralstat is administered orally, allowing for people with HAE to treat attacks at attack recognition.^[1]

Society and culture

Legal status

Sebetralstat was approved in the US by the FDA in July 2025 for the on-demand treatment of hereditary angioedema in adults and children aged 12 years of age and older. Regulatory submissions for approval in the European Union (EU) and other regions are ongoing. The drug is marketed as EKTERLY by KalVista Pharmaceuticals.^[2]