Phase 3 Data Supports Sebetralstat Efficacy for HAE Attacks Ahead of PDUFA Date

Oral sebetralstat was able to be rapidly administered and provided quick symptom relief in adolescents with hereditary angioedema (HAE- C1INH).1

These findings, from the phase 3 KONFIDENT (NCT05259917) and KONFIDENT-S open-label extension (NCT05505916) trials, will be presented at the 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress, February 28-March 3, in San Diego, California, by Danny Cohn, MD, PhD, Amsterdam UMC, University of Amsterdam.

“Adolescents with HAE C1INH often delay or withhold parenteral on-demand treatment after attack onset. Oral on-demand treatment could facilitate early treatment, reduce treatment burden associated with parenteral on-demand agents, and improve outcomes. This analysis was conducted to investigate time to administration, efficacy, and safety of oral sebetralstat in adolescents with HAE-C1INH,” Cohn and colleagues wrote.1

This analysis pooled together data from attacks treated with sebetralstat 600 mg by adolescents (12-17 years) in KONFIDENT and KONFIDENT-S. Investigators evaluated the time to beginning of symptom relief, time to reduction in attack severity (both within 12 hours), and time to complete resolution within 24 hours.

The data, current as of January 31, 2024, are from 19 adolescents with HAE-C1INH-Type1 and a mean age of 15.3 years (range, 13-17). These adolescents treated 149 HAE attacks (median, 4; range, 1-34), 33 (22.1%) of which were mild, 50 (33.6%) of which were moderate, 51 (34.2%) of which were severe, and 14 (9.4%) of which were very severe at baseline. Of these attacks, 68 were mucosal (including 1 laryngeal) and 81 were subcutaneous only.1

Cohn and colleagues found that the median time from attack onset to treatment was 4.0 minutes (IQR, 1.0-52.0). The median time to beginning of symptom relief was 1.79 hours (range, 0.76-7.12), to reduction in severity was 3.53 hours (range, 0.81->12), and to complete attack resolution was 15.09 hours (range, 3.52->24). The investigators reported 12 treatment-emergent adverse events (AE) in 6 adolescents (31.6%); 1 AE of tremor in 1 participant was treatment related. There were no study discontinuations.1

The positive data may support a potential approval of sebetralstat, an investigational oral plasma kallikrein inhibitor, which could offer a new mode of oral administration for HAE treatments given the availability of primarily injectable treatments as the most efficient manner of addressing swelling attacks from HAE.

KalVista Pharmaceuticals announced in September 2024 that the FDA had accepted its new drug application (NDA) for sebetralstat for review for the on-demand treatment of HAE attacks in adult and pediatric patients aged 12 years and older, with a Prescription Drug User Fee Act (PDUFA) goal date of June 17, 2025.2

“We are thrilled with the FDA’s acceptance of our NDA for sebetralstat as it moves us one step closer to bringing a potentially transformative therapy to the HAE community,” Ben Palleiko, Chief Executive Officer at KalVista, said in a previous statement.2 “We understand that people living with HAE and their families carry a tremendous burden every day as they don’t know when the next attack may occur or if the attack could cause life-threatening consequences. The compelling data included in our NDA package show that sebetralstat has the potential to significantly alter the way people treat and manage their disease. Given that it could be the first, oral on-demand treatment for HAE, we continue to receive strong support and hear a sense of urgency among healthcare providers, advocates, patients and their families for sebetralstat. I am proud of the team at KalVista for their dedication to achieving this milestone and deeply grateful for the support of patients living with HAE, their families, the HAE scientific community, and the HAEA and HAEi patient advocacy organizations.”

REFERENCES
1. Cohn D, Kessell A, Kinaciyan T, et al. On-demand Treatment Of Hereditary Angioedema Attacks With Sebetralstat In Adolescents: Pooled Analysis From KONFIDENT And KONFIDENT-S. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 552.

2. KalVista Announces FDA Acceptance of New Drug Application for Sebetralstat for Oral On-Demand Treatment of Hereditary Angioedema. News release. KalVista. September 3, 2024. https://ir.kalvista.com/news-releases/news-release-details/kalvista-announces-fda-acceptance-new-drug-application