Sebetralstat

Sebetralstat is a competitive, reversible inhibitor of plasma kallikrein. Plasma kallikrein is a serine protease that cleaves high molecular weight kininogen (HK) releasing bradykinin which increases vascular permeability through activation of bradykinin receptors causing edema.

• EKTERLY® is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. EKTERLY ® is a plasma kallikrein inhibitor indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older.

• None.contraindicated

Recommended Dosage : one dose of 600 mg (2 tablets) taken orally at the earliest recognition of an HAE attack. ( 2.1 ) A second dose of 600 mg (2 tablets) may be taken 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. ( 2.1 ) Maximum Recommended Dosage: 1,200 mg in any 24-hour period. ( 2.1 ) See full prescribing information for dosage modification for concomitant use with CYP3A4 inhibitors and inducers. ( 2.2 ) See full prescribing information for recommended dosage for patients with hepatic impairment. ( 2.3 ) 2.1 Recommended Dosage The recommended dosage of EKTERLY is one dose of 600 mg (two tablets) orally at the earliest recognition of an acute HAE attack. A second dose of 600 mg (two tablets) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. Maximum recommended dosage is 1,200 mg (four tablets) in any 24-hour period. 2.2 Dosage Modification for CYP3A4 Inhibitors and Inducers Refer to Table 1 for dosage modification of EKTERLY when used concomitantly with CYP3A4 inhibitors and inducers. Table 1: Dosage Modification of EKTERLY for Concomitant use with CYP3A4 Inhibitors and Inducers Dosage Modification for Concomitant use of EKTERLY with CYP3A4 Inhibitors Strong CYP3A4 Inhibitors Avoid concomitant use with EKTERLY. Moderate CYP3A4 Inhibitors Reduce EKTERLY dosage to 300 mg (one tablet) orally at earliest recognition of an acute HAE attack.

The most common adverse reaction (incidence ≥2%) is headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact KalVista Pharmaceuticals, Inc. at 1-855-258-4782 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of EKTERLY is based on data from a double-blind, randomized, placebo-controlled, three-way, crossover clinical trial (KONFIDENT) [see Clinical Studies ( 14 )] . In KONFIDENT, a total of 110 patients aged 12 years and older with HAE treated 264 attacks. In the safety population, 93 patients received EKTERLY 600 mg, 86 patients received EKTERLY 300 mg, and 83 patients received placebo. While EKTERLY 300 mg was included in KONFIDENT, the safety data is based on the recommended dosage of EKTERLY 600 mg. Table 3 displays adverse reaction(s) with an incidence of ≥2% in the EKTERLY 600 mg treated patients and more common than placebo. Table 3: Adverse Reaction(s) with EKTERLY with Incidence ≥2% and More Common than Placebo in Patients with Hereditary Angioedema (KONFIDENT) a One (1) patient assigned to administer placebo actually received EKTERLY 600 mg. Safety results are presented by actual treatment received. Adverse Reaction EKTERLY 600 mg (N = 93) Placebo (N = 83) a n (%) n (%) Headache 3 (3.2) 1 (1.2)

Hepatic Impairment : Avoid use of EKTERLY in patients with severe hepatic impairment (Child-Pugh Class C). In patients with moderate hepatic impairment (Child-Pugh Class B) take one dose of 300 mg. A second dose of 300 mg may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. ( 2.3 , 8.6 , 12.3 ) 8.1 Pregnancy Risk Summary There are no available data on EKTERLY in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of sebetralstat to pregnant rats and rabbits during organogenesis produced no evidence of fetal harm with dose exposures up to approximately 15 and 11 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of up to 1,200 mg (on an area under the curve [AUC] basis). Sebetralstat produced an increase in embryofetal losses and fetal malformations in rats at an exposure that was 60 times the MRHD (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.

Metabolism

Following a single oral dose of 600 mg sebetralstat in subjects with HAE, the geometric mean (CV%) C max is 6,080 ng/mL (40%) and AUC 0-inf is 17,600 ng•h/mL (36%). Following administration of a second oral dose of 600 mg sebetralstat 3 hours after the first dose, C max increases 10% and AUC 0-inf increases 90% when compared to those observed following a single dose.

Consider contacting the poison control help line (1-800-222-1222) or medical toxicologist for overdose management recommendations.

• Jul 3, 2025NDANDA219301Kalvista

1. 1Hereditary Angioedema6136%
2. 2Drug Ineffective2515%
3. 3Headache148.2%
4. 4Product Dose Omission Issue127.0%
5. 5Weight Increased105.8%
6. 6Stress84.7%
7. 7Insurance Issue74.1%
8. 8Off Label Use74.1%
9. 9Dizziness63.5%
10. 10Hypersensitivity63.5%
11. 11Incorrect Dose Administered63.5%
12. 12Nausea63.5%
13. 13Weight Decreased63.5%
14. 14Incorrect Dosage Administered52.9%
15. 15Product Use Issue52.9%

The 8 most recently updated of 8 ClinicalTrials.gov registrations naming Sebetralstat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• PK Subtrial in Adolescent Patients With HAE Type I or II Participating in the KVD900-302 Trial
  Completed · Phase 3 · Interventional · 11 enrolled · KalVista Pharmaceuticals, Ltd.
  NCT05511922updated 2026-06-08
• An Open-label Extension Trial to Evaluate the Long-term Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)
  Completed · Phase 3 · Interventional · 145 enrolled · KalVista Pharmaceuticals, Ltd.
  NCT05505916updated 2026-06-05
• Treatment of Angioedema Attacks in Pediatric (Ages 2-11) Post-Trial and Naive Patients With HAE With Sebetralstat
  Available · Expanded access · KalVista Pharmaceuticals, Ltd.
  NCT07216378updated 2026-05-28
• Open-Label Safety, PK, and Efficacy Trial of Sebetralstat (KVD900) in Pediatric Patients (Ages 2-11) With HAE Type I or II
  Completed · Phase 3 · Interventional · 36 enrolled · KalVista Pharmaceuticals, Ltd.
  NCT06467084updated 2026-01-23
• Treatment of Angioedema Attacks in Adolescent and Adult Patients 12 Years and Older With HAE Type I or II With Sebetralstat
  Approved for marketing · Expanded access · KalVista Pharmaceuticals, Ltd.
  NCT06628713updated 2025-08-06
• A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)
  Completed · Phase 3 · Interventional · 136 enrolled · KalVista Pharmaceuticals, Ltd.
  NCT05259917updated 2025-05-02
• A Phase II, Cross-over Clinical Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) in the On-demand Treatment of Angioedema Attacks in Adult Subjects With Hereditary Angioedema Type I or II
  Completed · Phase 2 · Interventional · 84 enrolled · KalVista Pharmaceuticals, Ltd.
  NCT04208412updated 2025-05-02
• A Single Dose Safety, Tolerability, Pharmacokinetic and Food Effect Study of KVD900 (Sebetralstat) in Healthy Volunteers
  Completed · Phase 1 · Interventional · 84 enrolled · KalVista Pharmaceuticals, Ltd.
  NCT04349800updated 2025-04-29

Frequently asked questions

How does Sebetralstat work?

Sebetralstat is a competitive, reversible inhibitor of plasma kallikrein. Plasma kallikrein is a serine protease that cleaves high molecular weight kininogen (HK) releasing bradykinin which increases vascular permeability through activation of bradykinin receptors causing edema.

What is Sebetralstat used for?

According to FDA labeling, Sebetralstat carries indications including: EKTERLY® is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. EKTERLY ® is a plasma kallikrein inhibitor indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Sebetralstat?

Sebetralstat is classified as Drugs used in hereditary angioedema, Plasma Kallikrein Inhibitor, Kallikrein Inhibitors, Decreased Bradykinin Production, Decreased Vascular Permeability.

What are the brand names for Sebetralstat?

Sebetralstat is marketed under brand names including Ekterly.

What are the contraindications for Sebetralstat?

Sebetralstat labeling lists contraindications including: None.. Always consult the full prescribing information and a clinician.