FDA approves Sebetralstat-Ekterly to treat angioedema

Sebetralstat (Sebetralstat)-Ekterly is now approved by the U.S. Food and Drug Administration for the on-demand treatment of hereditary angioedema, its span> Supporting data from the Phase 3, double-blind, three-way crossover KONFIDENT trial (NCT05259917) and its open-label extension KONFIDENT-S (NCT05505916) form the basis for this indication. Patients need to be 12 years or older to receive treatment.

This approval is particularly important because it means that a plasma kallikrein inhibitorsebetralstat is not only the first and only oral, on-demand treatment specifically for hereditary angioedema attacks, but also the first new on-demand treatment option approved for hereditary angioedema in more than 10 years. This is also the second approval of a drug for the treatment of hereditary angioedema in less than 3 weeks, following the approval of garadacimab gxii (Andembry; CSL) for once-monthly self-subcutaneous injection on June 16.

Until now, on-demand treatments have relied on subcutaneous or intravenous injections, which often resulted in delays in intervention. In the KONFIENT trial, 136 patients with hereditary angioedema were recruited from 66 sites in 20 countries. They were randomly assigned to sebetralstat (then known as KVD900), given as two 300 mg tablets (600 mg total) or one 300 mg tablet (300 mg), with the primary outcome being time to symptom relief as measured by the Patient Global Impression of Change Scale within 12 hours after the first dose. Secondary outcomes were time from baseline to first incidence reduction and time to complete resolution of hereditary angioedema episodes, both measured by global patient severity score.

Previously published data showed that sebetralstat resulted in symptom relief, less severe attack severity, and complete resolution of attacks more quickly than with placebo. KONFIDENT results published last year showed that the median (IQR) time to first symptom relief with sebettralstat was 1.61 hours (0.78-7.04) and 1.79 hours (1.02-3.79) at doses of 300 mg (P < .001) and 600 mg (P = .001), respectively, compared with 6.72 hours (1.34 to >12) for placebo. The corresponding incidence rates of complete remission within 24 hours were 42.5%, 49.5%, and 27.4%, respectively. Overall, the drug was well tolerated and had a safety profile similar to placebo.

New data from KONFIENT-S show that for hereditary angioedema attacks that specifically involve the throat or abdomen, and for breakthrough attacks if long-term prophylaxis is used, the time to initial symptom relief is shorter at 1.3 hours, and patients can self-treat within 10 minutes. Additionally, patients taking the 600 mg dose demonstrated a similar safety profile across more than 1,700 episodes, which was "consistent with that observed in KONFIDENT."

It was previously reported that in the VANGUARD Phase 3 trial (NCT04656418), the two newly approved drugs complement each other and can be used in combination, with sebtralstat "very good" as a relief drug for treating attacks and garadacimab as a long-term preventive drug.

Reference materials:https://www.ekterly.com/