Sebetralstat Shows Promise as First Oral Treatment for HAE Attacks, Including Breakthrough Episodes During Prophylaxis
Key Insights
New data from the KONFIDENT-S (search) trial demonstrates sebetralstat's effectiveness in treating HAE (search) attacks, with patients achieving symptom relief within 1.3 hours and treatment initiation within 6-20 minutes.
Sebetralstat proved well-tolerated in patients receiving various long-term prophylaxis treatments, including berotralstat, potentially transforming HAE (search) management for those preferring needle-free options.
KalVista Pharmaceuticals awaits FDA review of sebetralstat with a PDUFA date of June 17, 2025, positioning it to potentially become the first oral on-demand treatment for HAE (search) patients aged 12 and older.
KalVista Pharmaceuticals has presented compelling new data for sebetralstat, their investigational oral plasma kallikrein inhibitor, at the Western Society of Allergy, Asthma & Immunology (search) 2025 Annual Meeting, demonstrating its potential as a groundbreaking treatment for hereditary angioedema (search) (HAE (search)) attacks.
Efficacy in Treating Breakthrough Attacks
The interim analysis from the KONFIDENT-S (search) open-label study revealed significant efficacy in treating HAE (search) attacks, even in patients receiving long-term prophylaxis (LTP). Participants treated 382 attacks with sebetralstat, averaging 1.7 attacks per month. The drug enabled rapid treatment initiation, with a median time of 6 minutes to administration and symptom relief achieved within a median of 1.3 hours.
Dr. Riedl, a key investigator, emphasized, "Treatment guidelines recommend that patients with HAE (search) should consider treating all attacks regardless of LTP use and should treat attacks as early as possible. These interim results suggest that, if approved, sebetralstat could be a safe and effective oral on-demand treatment for breakthrough attacks."
Performance with Berotralstat Prophylaxis
Dr. Michael E. Manning, Past President of WSAAI, presented specific data on sebetralstat's performance in patients receiving berotralstat prophylaxis. These participants treated 178 attacks (mean 1.8 attacks per month) with sebetralstat, achieving treatment initiation within 20 minutes and symptom relief within 1.3 hours. Notably, the treatment showed no increase in gastrointestinal side effects.
"In general, patients prefer oral treatments over injectables," Dr. Manning noted. "These results demonstrate that sebetralstat could transform the treatment landscape for physicians and patients who prefer to manage HAE (search) without needles."
Clinical Development Status
The drug's development program includes the KONFIDENT (search) phase 3 trial, which enrolled 136 patients across 66 clinical sites in 20 countries, making it the largest HAE (search) clinical trial to date. The ongoing KONFIDENT-S (search) extension trial is evaluating long-term safety and efficacy, with plans to transition to a novel oral disintegrating tablet formulation supporting a planned 2026 sNDA filing.
Potential Impact on HAE Management
Dr. Paul Audhya, Chief Medical Officer of KalVista, highlighted the limitations of current injectable treatments: "Injectable on-demand treatments have side effects and logistical obstacles that hinder adequate disease control and drive an over-reliance on LTP. Sebetralstat has the potential to enable early treatment of attacks, thereby halting progression at an early stage and reducing morbidity."
With regulatory reviews underway at the FDA, EMA, and other global authorities, and a PDUFA date of June 17, 2025, sebetralstat could soon become the first oral, on-demand treatment option for HAE (search) patients aged 12 and older, potentially revolutionizing the management of this rare genetic disease.