First Oral On-Demand Therapy for Hereditary Angioedema Now Available: KalVista's sebetralstat Marks a Decade of Medical Progress

Hereditary angioedema (HAE) patients have historically faced a significant challenge: managing unpredictable and potentially life-threatening attacks required intravenous or subcutaneous injections. This treatment burden changed dramatically with the FDA’s approval of a novel plasma kallikrein inhibitor developed by KalVista Pharmaceuticals—EKTERLY (sebetralstat)—marking the first oral on-demand medication for this rare genetic disorder in over ten years.

Why This Approval Matters for HAE Management

The clinical evidence supporting sebetralstat’s approval is compelling. The KONFIDENT phase 3 trial, the largest clinical study ever conducted in HAE, enrolled 136 patients across 66 sites in 20 countries. Results published in the New England Journal of Medicine demonstrated that EKTERLY achieved significantly faster symptom relief, reduced attack severity, and achieved resolution faster than placebo—with a safety profile comparable to placebo itself.

Real-world data from the KONFIDENT-S open-label extension trial revealed even more promising outcomes. By September 2024, patients treated with sebetralstat were able to administer medication in a median of just 10 minutes after symptom onset. For the most severe presentations—laryngeal swelling, abdominal attacks, and breakthrough attacks despite prophylactic therapy—symptom relief began in approximately 1.3 hours, regardless of attack location or patient age.

Transforming Patient Independence and Quality of Life

What distinguishes EKTERLY from previous on-demand treatments is not merely efficacy, but accessibility. Prior therapies required medical administration—a burden that delayed treatment and limited patients’ ability to respond immediately to attacks. Sebetralstat’s oral formulation empowers individuals to treat attacks independently, whenever and wherever symptoms emerge.

“This is particularly meaningful for people who experience breakthrough attacks despite using long-term preventive therapy,” noted clinical researchers involved in the KONFIDENT investigation. “Having an immediate, self-administered option aligns with modern treatment philosophy: intervening early to prevent swelling progression and reduce overall disease burden.”

The medication is approved for patients aged 12 and older, with ongoing pediatric studies examining its use in younger children. Safety monitoring across more than 1,700 treatment instances in KONFIDENT-S confirmed a consistent tolerability profile, with headache being the most commonly reported side effect.

Addressing a Persistent Unmet Need

Despite prophylactic options, most HAE patients experience unpredictable attacks requiring ready access to acute treatment. The shift from injection-dependent therapy to oral self-administration represents a qualitative change in disease management—one that supports early intervention and reduces the anxiety associated with limited treatment access.

KalVista has launched sebetralstat in the U.S. market immediately, with physicians able to prescribe EKTERLY beginning today. The company has established a comprehensive patient support program to assist eligible individuals with insurance navigation, coverage access, and ongoing support throughout treatment.

Multiple regulatory applications for sebetralstat remain under review in key international markets, positioning this therapy as a potential foundational treatment for HAE management worldwide.