Sebetralstat Shows QoL Gains on Top of HAE Prophylaxis in KONFIDENT-S

Quality of life (QoL) scores improved over 15 months in patients with hereditary angioedema (HAE) who treated breakthrough attacks with sebetralstat while on long-term prophylaxis (LTP), according to the recent KONFIDENT-S open-label extension analysis.^1,2 Investigator Daniel F. Soteres, MD, MPH, a physician from Asthma & Allergy Associates, PC, discussed what those gains mean for patients already considered well-controlled.

“When you think about using a new medication, we want to know: Is it safe? Is it effective? And then our patients definitely want to know…what will it offer them in terms of improvement in their quality of life,” Soteres said.

The analysis included 35 participants with type 1 HAE who experienced a total of 504 breakthrough attacks despite being on a long-term prophylaxis of either berotralstat (n = 16), lanadelumab (n = 13), or C1 inhibitor replacement (n = 6). With sebtralstat, the median time to the beginning of symptom relief was 1.3 hours for both berotralstat and lanadelumab and 1.8 hours for C1 inhibitor LTP.¹ Only 1.6% of the breakthrough attacks went untreated, and 22.3% of attacks required a second dose of sebtralstat within 12 hours.

The median time from attack recognition to sebetralstat administration was 6 minutes overall. This ranged from 1 minute in participants on C1 inhibitor LTP to 20 minutes in those on berotralstat. In this study, nearly 30% of attacks were treated while still mild.

Sebetralstat Improves Quality of Life in HAE

QoL scores were available for 34 participants. Among these patients, Angioedema Quality of Life Instrument scores improved by a squares mean of 10.3 points (−21.1 to 0.6) from baseline to month 15, exceeding the threshold considered clinically meaningful. The largest gains were in the fatigue/mood (-13.3), followed by gains in fears/shame (-11.2) and functioning (-9.6).¹ Treatment satisfaction was high, with 88.8% of sebetralstat-treated attacks rated satisfactory and 75.0% rated very or extremely satisfactory.¹

The Smaller C1 Inhibitor Subgroup in KONFIDENT-S

Effectiveness signals looked somewhat different among the 6 participants receiving C1 inhibitor (C1INH) LTP, whose median time to complete attack resolution was 16.6 hours versus 10.9 hours for berotralstat and 15.1 hours for lanadelumab.¹ Soteres cautioned against overinterpreting the small subgroup, noting patients on C1INH may be more accustomed to relief from injectable therapies, representing "a real paradigm shift" in understanding that a pill could offer comparable results. He added there could also be subtle differences in disease chemistry that respond more slowly, though efficacy still held for these patients.

Soteres said the findings reinforce existing guidance rather than change it: patients with HAE, including those stable on LTP, should keep 2 doses of on-demand therapy available at all times, a standard he has built into his own practice. He said sebetralstat's oral route remains a favorable on-demand option even for patients who continue to have it available alongside injectable choices.

Read part 1 of our interview with Soteres here: Sebetralstat Resolves Breakthrough HAE Attacks Despite Prior Prophylaxis.³

Editor’s note: Reported disclosures for Soteres include KalVista Pharmaceuticals, BioCryst, CSL Behring, Intellia Therapeutics, Ionis Pharmaceuticals, Pharming, Pharvaris, and Takeda.

References

1. Kinaciyan T, Aygören-Pürsün E, Martinez-Saguer I, et al. Sebetralstat for breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis in KONFIDENT-S. J Allergy Clin Immunol Glob. 2026;5(5):100750. Published 2026 Jun 12. doi:10.1016/j.jacig.2026.100750

2. Johnson V. Sebetralstat Shows Long Term Fast Relief of Breakthrough HAE Attacks. HCPLive. Published July 21, 2026. Accessed July 24, 2026. https://www.hcplive.com/view/sebetralstat-shows-long-term-fast-relief-breakthrough-hae-attacks

3. Soteres D. Sebetralstat Resolves Breakthrough HAE Attacks Despite Prior Prophylaxis. HCPLive. Published July 24, 2026. Accessed July 24, 2026. https://www.hcplive.com/view/sebetralstat-resolves-breakthrough-hae-attacks-prior-prophylaxis