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Sebetralstat (Ekterly)
Sebetralstat (Ekterly) is a real, recently FDA-approved oral kallikrein inhibitor that gives this site's hereditary angioedema (HAE) cluster its missing on-demand counterpart to berotralstat's daily prophylaxis — the first oral pill of any kind approved to treat an HAE attack once it starts, rather than prevent one in advance. Approved 3 July 2025 on a real placebo-controlled Phase 3 trial, it's a genuinely new option in a cluster this site has otherwise covered as injectable-only for acute treatment.
On this page
In brief
Should you care? Relevant if hereditary angioedema is a live concern and treating an attack with a pill, rather than a self-injection, matters to you — the newest drug in this site's HAE cluster and the first oral option approved specifically for acute attacks rather than daily prevention.The short version
- What it is: a small-molecule (non-peptide) oral inhibitor of plasma kallikrein — the same enzyme this site's ecallantide page describes a single-dose injectable protein blocking, and the same target this site's berotralstat page's daily pill also inhibits — but taken only when an attack starts, not every day.
- KONFIDENT, the largest HAE trial ever run (136 patients, 66 sites, 20 countries): symptom relief began at a median of 1.61 hours on a 300mg dose and 1.79 hours on 600mg, both faster than placebo's 6.72 hours — the FDA-approved standard dose is the higher of the two, 600mg (two tablets).
- Approved 3 July 2025 — the first and, as of this review, only oral on-demand treatment ever approved for HAE attacks.
The one oral, on-demand drug in this site's HAE cluster
This site's hereditary angioedema (HAE) cluster — icatibant, ecallantide, conestat alfa, Berinert & Cinryze, lanadelumab & garadacimab, and berotralstat — splits into two jobs: stopping an attack already underway, and preventing attacks from starting at all. Every one of this site's acute, on-demand treatments for an active attack (icatibant, ecallantide, Berinert, Cinryze) is a self-injection or infusion; berotralstat is oral, but only for daily prevention. Sebetralstat, developed by KalVista Pharmaceuticals, fills the one remaining gap: a small-molecule, non-peptide oral tablet that inhibits plasma kallikrein — the same enzyme ecallantide and berotralstat both target — taken specifically at the first sign of an attack rather than every day. The FDA approved it on 3 July 2025 as the first oral, on-demand treatment ever approved for acute HAE attacks in patients 12 and older.
The KONFIDENT trial
Sebetralstat's approval rested on KONFIDENT (Lumry WR, Bernstein JA, Craig T, et al., "Oral Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks," N Engl J Med 2024;391(1):32-43, PMID 38819658, DOI: 10.1056/NEJMoa2314192), a randomized, double-blind, event-driven crossover Phase 3 trial that enrolled 136 adult and adolescent HAE patients across 66 sites in 20 countries — described by the trial investigators as the largest clinical trial ever conducted for this indication. Patients treated qualifying attacks with sebetralstat (300mg or 600mg) or placebo, crossing over to treat a separate attack with a different assignment. The median time to beginning of symptom relief was 1.61 hours with the 300mg dose and 1.79 hours with 600mg, versus 6.72 hours on placebo — both doses reaching statistical significance on the trial's primary endpoint, along with faster reductions in attack severity and time to complete attack resolution. The dose that went on to become the FDA-approved standard regimen is the higher of the two tested, 600mg (two 300mg tablets), taken as a single dose at the first sign of an attack.
How it differs from berotralstat
Same target, opposite job
Berotralstat and sebetralstat both inhibit plasma kallikrein by mouth, but they're not interchangeable or competing for the same use: berotralstat is a once-daily pill meant to lower how often attacks happen in the first place, while sebetralstat is taken only when an attack has already started — one 600mg dose (two tablets), with a second 600mg dose available after 3 hours if the response is inadequate or symptoms recur, up to 1,200mg in any 24-hour period. A patient on daily berotralstat prophylaxis can still have a breakthrough attack and separately need an on-demand treatment like sebetralstat — the two drugs address different points in the same disease course, the same relationship this site's icatibant and ecallantide pages describe against the older injectable on-demand options. A lower 300mg starting dose is used instead for patients with moderate hepatic impairment.
Current status
Ekterly has been commercially available in the US since shortly after its July 2025 approval, marketed by KalVista Pharmaceuticals. As a very recently approved specialty drug, its longer-term real-world safety and uptake data are still accumulating — worth checking a current source if that matters to you. There is no wellness, off-label bodybuilding or grey-market interest in sebetralstat of any kind we could find, consistent with every other drug in this site's HAE cluster: a specialty-prescribed treatment for a rare genetic disorder, not something with appeal outside that population.
References
- Lumry WR, Bernstein JA, Craig T, et al., "Oral Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks," N Engl J Med 2024;391(1):32-43, PMID 38819658, DOI: 10.1056/NEJMoa2314192 — the KONFIDENT trial, 136 patients across 66 sites in 20 countries.
- FDA approval of Ekterly (sebetralstat), 3 July 2025, for on-demand treatment of HAE attacks in patients 12 years and older (KalVista Pharmaceuticals; NDA 219301); FDA-approved prescribing information, Dosage and Administration — standard dose 600mg (two 300mg tablets), optional second 600mg dose after 3 hours, maximum 1,200mg/24 hours; reduced 300mg starting dose for moderate hepatic impairment.
- KalVista Pharmaceuticals press release, "KalVista Pharmaceuticals Announces FDA Approval of EKTERLY (sebetralstat), First and Only Oral On-demand Treatment for Hereditary Angioedema," 3 July 2025.