The FDA has approved sebetralstat, a plasma kallikrein inhibitor, as the first FDA-approved oral on-demand treatment for acute attacks of hereditary angioedema in patients aged 12 years and older, according to KalVista Pharmaceuticals. Ekterly is the first new on-demand hereditary angioedema therapy approved in more than a decade and the only non-injectable option currently available in the United States.

Approval was based on the phase 3 KONFIDENT trial, which randomized 136 patients from 66 sites in 20 countries. Sebetralstat was associated with significantly faster symptom relief, reduction in attack severity, and attack resolution compared with placebo. The treatment was well tolerated, with a safety profile comparable to placebo. These results were published in The New England Journal of Medicine in May 2024. In the KONFIDENT-S open-label extension trial, patients initiated treatment a median of 10 minutes after symptom onset. Median time to symptom relief was 1.3 hours among laryngeal, abdominal, and breakthrough attacks in patients receiving prophylaxis.

Prior to this approval, all FDA-approved on-demand hereditary angioedema treatments required intravenous or subcutaneous administration. The oral formulation enables more immediate treatment initiation, which aligns with current guidelines recommending early intervention for all attacks to prevent progression and reduce morbidity.

Headache was the most common adverse event reported. The safety profile of 600 mg sebetralstat was confirmed across >1700 attacks in the KONFIDENT-S extension. Clinicians are advised to review potential drug–drug interactions prior to prescribing, particularly with itraconazole, phenytoin, or efavirenz. Safety in pregnancy and lactation has not been established.

Full prescribing information is available at ekterly.com.

Source: KalVista Pharmaceuticals, Inc