Clinical Data
In the OPuS-2 study, HAE patients with a historical attack frequency of greater than 0.45 attacks per week were randomized to treatment with either 500 mg or 300 mg of avoralstat, or placebo, administered three times daily for 12 weeks. The primary goals of the trial were to characterize the efficacy of avoralstat in reducing the frequency of angioedema attacks, and to evaluate the safety and tolerability of 12 weeks of avoralstat treatment. The primary efficacy endpoint was angioedema attack frequency.Thirty-eight subjects received avoralstat 500 mg, 36 subjects received avoralstat 300 mg, and 36 subjects received placebo. Treatment with 500 mg and 300 mg of avoralstat three times daily failed to demonstrate a statistically significantly lower mean attack rate versus placebo. The mean (standard deviation) attack rates per week were 0.63 (0.57) on avoralstat 500mg, 0.71 (0.66) on avoralstat 300mg, compared to 0.61 (0.41) on placebo.


Secondary efficacy endpoints included measures of quality of life, attack duration and attack severity. Statistically significant improvements in duration of attacks and in the Angioedema Quality of Life total score, and its domains, were observed comparing the 500 mg three times a day avoralstat arm to placebo.

Oral administration of avoralstat in OPuS-2 was generally safe and well tolerated; the adverse event profile was similar to that for placebo; and no safety signals were observed.