Ekterly (sebetralstat) / KalVista, Kaken Pharma - LARVOL DELTA

Safety and Effectiveness of Sebetralstat (KVD900) for Short-Term Prophylaxis Before Procedures in People With Hereditary Angioedema (KONTROL) (clinicaltrials.gov) - P4 | N=100 | Recruiting | Sponsor: KalVista Pharmaceuticals, Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Attack-Related Anxiety Relief Should Not Be Equated With Treatment of an Anxiety Disorder. (PubMed, Clin Exp Allergy) - No abstract available

Journal • Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Hereditary Angioedema • Mood Disorders • Psychiatry

Evaluating deucrictibant for the treatment of hereditary angioedema. (PubMed, Expert Opin Pharmacother) - "Over the past 6 years two oral therapies have been developed for HAE to include berotralstat for long term prophylaxis (LTP) and sebetralstat for on-demand therapy (ODT). Deucrictibant is a promising therapeutic agent with a well-defined mechanism of action. Published and ongoing clinical studies demonstrate favorable safety, tolerability, and efficacy profiles for both LTP and ODT, offering a convenient oral alternative that may reduce treatment burden and improve patient quality of life."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pain • Rare Diseases

Current and future therapies for bradykinin-mediated angioedema (PubMed, Dermatologie (Heidelb)) - "On-demand treatment options include plasma-derived and recombinant C1 inhibitor (C1INH) concentrates, the bradykinin B2 receptor antagonist icatibant, and, more recently, the first orally available plasma kallikrein inhibitor, sebetralstat...LTP therapies include subcutaneous and intravenous C1INH preparations, the oral kallikrein inhibitor berotralstat, the anti-kallikrein monoclonal antibody lanadelumab, the factor XIIa inhibitor garadacimab, and the antisense oligonucleotide donidalorsen. Currently under development are the oral bradykinin B2 receptor antagonist deucrictibant, which is intended for both on-demand treatment and long-term prophylaxis in different formulations, long-acting antibodies, such as navenibart, and CRISPR/Cas9-based gene-editing therapies, such as NTLA-2002 with potential functional curative properties. In particular, orally available and long-acting therapies are expected to improve adherence, self-management, and quality of life in..."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Sebetralstat for breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis in KONFIDENT-S. (PubMed, J Allergy Clin Immunol Glob) - P3 | "This interim analysis of the KONFIDENT-S study evaluated long-term safety and effectiveness of oral sebetralstat 600 mg for attacks of hereditary angioedema with C1-inhibitor deficiency in participants receiving LTP with lanadelumab, berotralstat, or C1 inhibitor. Sebetralstat was well tolerated and enabled early on-demand treatment of attacks in patients with hereditary angioedema with C1-inhibitor deficiency receiving LTP. Treatment of breakthrough attacks with sebetralstat resulted in rapid symptom relief, reduction in attack severity, and complete attack resolution, regardless of LTP mechanism of action."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Ekterly (sebetralstat) for hereditary angioedema: the first FDA-approved oral on-demand therapy. (PubMed, Ann Med Surg (Lond)) - No abstract available

FDA event • Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Isolated angioedema in the emergency department: rarely an allergic reaction. (PubMed, Am J Emerg Med) - "Differentiating between these pathways is critical, as standard anaphylaxis treatments like epinephrine are often ineffective for non-allergic variants...Effective treatment requires a targeted approach based on the underlying mechanism, including antihistamines for histamine-mediated reactions and on-demand therapies for bradykinin-mediated hereditary angioedema, such as C1-esterase inhibitor concentrate, icatibant, and the recently approved oral kallikrein inhibitor sebetralstat. This article provides a clinical framework to help emergency physicians identify the correct underlying mechanism. Ultimately, accurate diagnosis facilitates appropriate specialist referral and improves long-term patient outcomes."

Journal • Review • Allergy • Cardiovascular • Chronic Spontaneous Urticaria • Complement-mediated Rare Disorders • Dermatology • Hereditary Angioedema • Immunology • Urticaria

Sebetralstat for on-demand treatment of hereditary angioedema: A pooled analysis of placebo-controlled clinical trials. (PubMed, World Allergy Organ J) - P2, P3 | "Across phase 2 and 3 clinical trials, sebetralstat enabled early treatment, provided effective symptom relief versus placebo, and was well tolerated, regardless of attack location or baseline severity. ClinicalTrials.gov Identifier NCT04208412, registered on 2019-07-02; ClinicalTrials.gov Identifier NCT05259917 (KONFIDENT), registered on 2022-02-22."

Clinical • Journal • Retrospective data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • STAT3

Diverse Trial Designs, Populations, and Outcomes: A Systematic Literature Review of Trials for the Treatment of Hereditary Angioedema Attacks. (PubMed, Adv Ther) - "Substantial heterogeneity in trial design, attack eligibility criteria, redosing and rescue protocols, censoring rules, and endpoint definitions limit cross-trial comparability of on-demand HAE therapies. Future comparative efficacy research should prioritize harmonization of endpoint definitions, map across PRO instruments, and adjust for treatment effect modifiers."

Clinical • Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hereditary Angioedema

Safety and Effectiveness of Sebetralstat for Short-Term Prevention Before Procedures in People With Hereditary Angioedema (clinicaltrials.gov) - P4 | N=100 | Not yet recruiting | Sponsor: KalVista Pharmaceuticals, Ltd.

New P4 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

PK Subtrial in Adolescent Patients With HAE Type I or II Participating in the KVD900-302 Trial (clinicaltrials.gov) - P3 | N=11 | Completed | Sponsor: KalVista Pharmaceuticals, Ltd. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

KONFIDENT-S: 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) (clinicaltrials.gov) - P3 | N=145 | Completed | Sponsor: KalVista Pharmaceuticals, Ltd. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

COST-EFFECTIVENESS OF RECOMBINANT HUMAN C1 ESTERASE INHIBITOR (RHC1-INH) VS SEBETRALSTAT FOR THE TREATMENT OF SEVERE OR VERY SEVERE HEREDITARY ANGIOEDEMA (HAE) ATTACKS (ISPOR 2026) - P2/3, P3 | "For severe or very severe HAE attacks, rhC1-INH treatment offers more attack-free time, cost savings, and QALH gains driven by faster time to complete resolution and reduced need for redosing compared with sebetralstat."

Cost effectiveness • HEOR • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Rare Diseases

Comparative Efficacy of Recombinant C1 Inhibitor Versus Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks: A Matching-Adjusted Indirect Treatment Comparison. (PubMed, Adv Ther) - "rhC1-INH provides significantly faster symptom resolution and lower redosing rates vs sebetralstat."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Status of Current Clinical Trials on Therapy for Hereditary Angioedema (IMMUNOLOGY 2026) - "The sole drug in phase 4 is CSL312 (Garadacimab), a fully human IgG4 monoclonal antibody targeting activated factor XIIa. Drugs in phase 3 include: NTLA-2002, a single-dose intravenous gene therapy targeting inactivation of the KLKB1 gene; Navenibart, an IgG1 monoclonal antibody inhibiting activated kallikrein; OCTA-C1-INH, a virus-inactivated, nanofiltrated, highly purified concentrate of C1-INH derived from pooled human plasma; ADX-324, an siRNA therapy to reduce hepatic production of prekallikrein (PKK); Donidalorsen, an antisense oligonucleotide targeted against hepatic PKK mRNA; Sebetralstat and berotralstat, both plasma kallikrein inhibitors that reduce production of bradykinin; and deucrictibant, a competitive bradykinin B2 receptor antagonist. Advances in gene therapy, biologics, RNA interference therapeutics, and improved replacement strategies hold promise for transforming both rescue and prophylactic management for HAE. Ongoing evaluation of safety,..."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Hereditary Angioedema • AVEN

Impact of Oral Sebetralstat on Anxiety Associated With Hereditary Angioedema Attacks. (PubMed, Clin Exp Allergy) - P3 | "Moderate-to-extreme anxiety was common in HAE attacks. Reduction in anxiety was significantly greater in attacks treated with sebetralstat compared with placebo."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Mood Disorders • Psychiatry • STAT3

On-demand Treatment Patterns of Hereditary Angioedema (HAE) Attacks with Sebetralstat in the KONFIDENT-S Study (AAAAI 2026) - "Conclusions Given that participants could utilize conventional treatment for attacks, the preference for sebetralstat for on-demand treatment of most attacks in KONFIDENT-S was evident. A greater proportion of attacks were treated in KONFIDENT-S compared to real-world observational studies, possibly due to reduced barriers to treatment with sebetralstat, leading to a higher willingness of participants to treat attacks; particularly attacks that were mild in severity."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Response Drivers in Sebetralstat Placebo-controlled Clinical Trials (AAAAI 2026) - "Using the final model, a simulation (n=5000) of a single sebetralstat 600mg dose administered within 30 minutes of attack onset provided symptom relief for 88.5% (95% CI: 81.2% - 93.9%) of simulation subjects within 12 hours. Conclusions In this modeling and simulation using placebo-controlled clinical trial data, time to treatment (<30 minutes) was the most robust driver of endpoint achievement, highlighting the importance of early treatment in accordance with treatment guidelines, and underscoring the value of oral on-demand treatment."

Clinical • Dermatology

The power of a pill: Ekterly (Sebetralstat): first oral on-demand therapy for hereditary angioedema-a paradigm shift in treatment. (PubMed, Ann Med Surg (Lond)) - No abstract available

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Sebetralstat (Ekterly) for treatment of hereditary angioedema attacks. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

KONFIDENT-KID: Open-Label Safety, PK, and Efficacy Trial of Sebetralstat (KVD900) in Pediatric Patients (Ages 2-11) With HAE Type I or II (clinicaltrials.gov) - P3 | N=36 | Completed | Sponsor: KalVista Pharmaceuticals, Ltd. | Recruiting ➔ Completed | Trial completion date: Aug 2027 ➔ Jan 2026 | Trial primary completion date: Aug 2027 ➔ Jan 2026

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pediatrics

Novel drug approval by the FDA: Ekterly (Sebetralstat), oral plasma kallikrein inhibitor for treating acute attacks of hereditary angioedema. (PubMed, Ann Med Surg (Lond)) - "Through a detailed appraisal of its therapeutic efficacy, safety profile, and pharmacologic constraints -including clinically relevant interactions with CYP3A4 modulators and the lack of evidence in pregnant patients or those with hepatic impairment ,this editorial emphasizes Ekterly's emerging role as an important and potentially transformative addition to HAE management.The approval of sebetralstat signals a new era of convenient, rapid-acting, accessible treatment for HAE, with the potential to reduce emergency visits, enhance patient autonomy, and improve quality of life. Continued surveillance, long-term safety studies, and global access initiatives will be essential to maximize its public-health impact and ensure equitable availability of this breakthrough oral therapy."

FDA event • Journal • Cardiovascular • Complement-mediated Rare Disorders • Hepatology • Hereditary Angioedema • Rare Diseases • CYP3A4

KalVista Pharmaceuticals Announces Approval of EKTERLY (sebetralstat) in Japan, First and Only Oral On-demand Treatment for Hereditary Angioedema (Businesswire) - "KalVista Pharmaceuticals, Inc...announced that the Ministry of Health, Labor and Welfare (MHLW) in Japan has granted marketing and manufacturing approval for EKTERLY (sebetralstat), a novel plasma kallikrein inhibitor, for the treatment of acute attacks of hereditary angioedema (HAE) in adults and adolescents aged 12 years and older...EKTERLY will be commercialized in Japan by KalVista’s partner, Kaken Pharmaceutical Co., Ltd. Kaken will launch EKTERLY shortly after it is listed on the Japanese National Health Insurance System (NHI)...The approval is based on results from the phase 3 KONFIDENT clinical trial..."

Japan approval • Launch Japan • Hereditary Angioedema

Sebetralstat as a patient-centered alternative to lanadelumab: Insights from recent real-world evidence. (PubMed, Ann Allergy Asthma Immunol) - No abstract available

HEOR • Journal • Real-world evidence

Assessing the Adoption of Novel Therapies in a Private/Public Payer System: A Study in Fitusiran, Sebetralstat, and Nipocalimab (ASHP 2025) - No abstract available