KalVista Pharmaceuticals announced compelling new clinical data demonstrating that sebetralstat, an investigational oral plasma kallikrein inhibitor, consistently halts hereditary angioedema (HAE) attack progression in a median time of 19.8 minutes. The findings were presented at the 14th C1-inhibitor Deficiency & Angioedema Workshop in Budapest, Hungary, and the Eastern Allergy Conference in Palm Beach, Florida, from May 29–June 1, 2025.
Rapid Attack Progression Control Across Clinical Programs
The time-to-end-of-progression analysis, presented by Dr. William Lumry from the University of Texas Southwestern Medical School, examined 1,591 attacks in the open-label extension study KONFIDENT-S. Results aligned closely with the pivotal phase 3 KONFIDENT trial, with both studies showing attack progression halted in a median of 19.8 minutes.
"Stopping the progression of an HAE attack as early as possible is paramount to mitigating its impact on patients," said Dr. Lumry. "In both the KONFIDENT and KONFIDENT-S studies, sebetralstat halted attack progression in a median time of 19.8 minutes. As prior data have demonstrated near-complete plasma kallikrein inhibition 15 minutes after treatment, this analysis reveals that attacks are halted minutes after absorption."
Efficacy in High-Risk Mucosal Attacks
Dr. Henriette Farkas from Semmelweis University presented interim data on sebetralstat's effectiveness against mucosal HAE attacks, which pose significant clinical concerns due to rapid progression risks and potential for asphyxiation if untreated. The analysis revealed that patients could self-administer sebetralstat quickly, with median treatment times of 20 minutes for abdominal attacks and 11.5 minutes for laryngeal attacks.
The median time to beginning of symptom relief was 1.3 hours for both abdominal and laryngeal attacks. Notably, 96% of attacks reaching symptom relief within 12 hours did so before or without requiring an additional sebetralstat administration. The drug was well-tolerated even in laryngeal attacks, with no reported difficulties swallowing the oral tablet.
"These interim data from KONFIDENT-S demonstrate that sebetralstat provided rapid relief and resolution of both abdominal and laryngeal attacks with a favorable safety profile," said Dr. Farkas. "Patients were able to self-administer sebetralstat very early in the course of an attack, when most attacks were still mild or moderate in severity."
Treatment of Severe and Delayed Attacks
Dr. H. Henry Li from the Institute for Asthma and Allergy presented data on sebetralstat's effectiveness in treating 76 attacks that had progressed to severe or very severe stages after a median of 2.16 hours from attack onset. These challenging scenarios demonstrated sebetralstat's utility even in advanced attack stages associated with delayed treatment.
The median time to beginning of symptom relief for these severe attacks was 1.36 hours, with reduction in attack severity occurring in a median of 1.77 hours and substantial reduction of symptom burden in 9.15 hours.
"When attacks are not treated early in accordance with guidelines, they can escalate and become severe," said Dr. Li. "Sebetralstat delivered symptom relief in a median time of 1.36 hours, reinforcing its potential as an on-demand treatment for challenging attack scenarios."
Regulatory Status and Clinical Significance
Sebetralstat is under regulatory review by the U.S. FDA, with a PDUFA goal date of June 17, 2025. KalVista has also completed Marketing Authorization Applications to the European Medicines Agency and multiple other global regulatory authorities. If approved, sebetralstat would become the first oral, on-demand treatment for HAE in individuals aged 12 and older, with ongoing studies exploring its use in children aged 2 to 11.
"These new data underscore the potential of sebetralstat to fundamentally change HAE attack management," stated Dr. Paul Audhya, Chief Medical Officer of KalVista. "Even in real-world, high-stakes scenarios—be it mucosal attacks or severe attacks due to delayed treatment—sebetralstat consistently delivered rapid and reliable relief. The uniformity of these results, paired with an oral tablet formulation, solidifies our belief that sebetralstat can empower patients to act swiftly and recover quickly."
Addressing Unmet Medical Need
Hereditary angioedema is a rare genetic disease resulting from deficiency or dysfunction in the C1 esterase inhibitor protein and subsequent uncontrolled activation of the kallikrein-kinin system. Patients experience painful and debilitating attacks of tissue swelling that can be life-threatening depending on the affected area. Currently, all approved on-demand treatment options require either intravenous or subcutaneous administration, highlighting the potential clinical advantage of an oral formulation.
