Sebetralstat for HAE


Sebetralstat is an oral plasma kallikrein inhibitor and the most advanced compound in our portfolio of candidates for the treatment of hereditary angioedema (HAE). Early treatment of HAE attacks has been shown to be key in maximizing treatment efficacy. Dosing with approved injectable treatments is often delayed undermining treatment outcomes. As a result of its straightforward oral administration combined with its rapid uptake and encouraging safety profile, sebetralstat has the potential to offer HAE patients an option to treat attacks at the earliest stages, before the symptoms develop more fully.

In March, 2022 we announced the initiation of the sebetralstat Phase 3 KONFIDENT clinical trial, evaluating the safety and efficacy of sebetralstat as an on-demand therapy for HAE attacks. KONFIDENT is a worldwide clinical study being conducted at approximately 60 sites in 20 countries. The trial is intended to enroll a minimum of 84 HAE adolescent and adult patients who will complete treatment of three attacks: one each with 300 mg sebetralstat, 600 mg sebetralstat and placebo in a double-blinded, randomized sequence. The primary endpoint of the trial is time to the beginning of symptom relief, evaluated on a Patient Global Impression of Change (PGI-C) scale, and additional endpoints will evaluate other measures of patient response and attack progression, as well as safety. We anticipate data from this trial in the second half of 2023 and, based upon the results of the trial, we expect to be able to file a NDA with the US FDA in the first half of 2024.

More information on the KONFIDENT study can be found at:

In February 2021, we reported positive results for a Phase 2 clinical trial demonstrating statistically and clinically significant responses for sebetralstat as an oral on-demand treatment for HAE attacks.

The sebetralstat Phase 2 was a randomized, double-blind, placebo-controlled, crossover clinical trial evaluating the efficacy and safety of sebetralstat as an on-demand treatment for hereditary angioedema (HAE) attacks. The trial completed 53 adult HAE patients from 25 clinical sites in the United States and Europe. The trial included type 1 and type 2 HAE patients who had three attacks in 90 days prior to enrollment. During the first part of the two-part trial, patients received a single, open label 600 mg dose of sebetralstat to evaluate pharmacokinetic and pharmacodynamic properties. All patients then entered part two of the trial, which was a double-blind investigation to assess the efficacy of sebetralstat compared to placebo in a two‑attack, crossover design. During part two of the trial, patients took a single dose of 600 mg of sebetralstat or placebo within one hour of the start of the first attack. The second attack was dosed with the alternative crossover treatment. Patients were able to use their conventional rescue treatment, as required.


Topline Phase 2 Results

  • Attacks treated with sebetralstat significantly reduced use of rescue (p=0.001), with 15% of sebetralstat treated attacks rescued compared to 30% on placebo at 12 hours. This efficacy benefit of sebetralstat was maintained at 24 hours (p=0.0005).

  • Sebetralstat significantly reduced time to onset of symptom relief (p=<0.0001) on a Patient Global Impression of Change scale (PGI-C), with a median time of 1.6 hours versus 9 hours for attacks treated with placebo.

  • Sebetralstat treated attacks achieved symptom relief more quickly than placebo treated attacks (p<0.0001) when assessed using a composite Visual Analogue Scale (VAS) score.

  • Within 12 hours of oral administration, sebetralstat significantly increased the number of stabilized or improved attacks when assessed by a Patient Global Impression of Severity scale (PGI-S) or use of rescue (p<0.0001).

  • Additional exploratory endpoints were also statistically significant and favored sebetralstat treatment over placebo.

  • There were no serious adverse events reported in the trial and no patients withdrew due to adverse events. In the open-label phase, 8 on-treatment drug-related treatment emergent adverse event (TEAE) were experienced by 5 patients. In the crossover phase of the trial, 3 on-treatment drug-related TEAEs were experienced by 3 patients (5.2%) following administration of sebetralstat, and 2 on-treatment drug-related TEAEs were experienced by 2 patients (3.6%) following administration of placebo.