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. The KONFIDENT Study is fully enrolled with top-line Phase 3 data results expected in the coming months. More information on the KONFIDENT study can be found at: www.konfidentstudy.com
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 93 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, for the first attack, patients took a single dose of 600 mg of sebetralstat or placebo within one hour of the start of the attack. The second attack was dosed with the alternative crossover treatment. Patients were able to use their conventional rescue treatment, as required.
(1) Aygören-Pürsün E, Zanichelli A, Cohn DM, Cancian M, Hakl R, Kinaciyan T, Magerl M, Martinez-Saguer I, Stobiecki M, Farkas H, Kiani-Alikhan S, Grivcheva-Panovska V, Bernstein JA, Li H, Longhurst HJ, Audhya PK, Smith MD, Yea CM, Maetzel A, Lee DK, Feener EP, Gower R, Lumry WR, Banerji A, Riedl MA, Mauer M. An investigational oral plasma kallikrein inhibitor foron-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial. Lancet 2023; 401: 458–69. DOI: 10.1016/S0140-6736(22)02406-0