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