Significant reduction in HAE attacks by 0.45 per week versus placebo (p < 0.001)
OPuS-1 evaluated 400 mg of BCX4161 administered three times a day for 28 days in HAE patients with a high attack frequency (≥ 1 per week), in a randomized, placebo-controlled, two-period cross-over design. The primary goals for the trial were to estimate the degree of efficacy of BCX4161 in reducing the frequency of angioedema attacks, and to evaluate the safety and tolerability of 28 days of BCX4161 treatment.
Twenty-four patients received study drug, and all completed the study. The primary efficacy endpoint for the trial was the by-subject difference in mean angioedema attack rate on BCX4161 compared to placebo. Treatment with BCX4161 demonstrated a statistically significant mean attack rate reduction of 0.45 attacks per week versus placebo, p < 0.001. The mean attack rate per week was 0.82 on BCX4161 treatment, compared to 1.27 on placebo.
Oral administration of BCX4161 was generally safe and well tolerated, with an adverse event profile similar to that observed for placebo. There was one serious adverse event reported, an abdominal HAE attack during the placebo period. Patient dosing compliance was 98 percent.
The mean number of attack-free days during each treatment period improved from 19 for placebo to 22 for BCX4161, p=0.008. Three subjects were attack-free during the BCX4161 period, compared to none during the placebo period. Quality of life was measured by the Angioedema Quality of Life questionnaire, AeQoL, and disease activity by the Angioedema Activity Score, AAS28. For BCX4161, the mean total AeQoL score improved by 8.4 units from baseline compared to 0.5 for placebo, p=0.004, and the AAS28 was 21.4 for BCX4161 compared to 28.8 for placebo, p=0.022.
Plasma drug concentrations and the degree of plasma kallikrein inhibition achieved after oral dosing with BCX4161 in OPuS-1 HAE patients were similar to those seen in healthy subjects in the Phase 1 trial. In OPuS-1, higher drug exposure was associated with a better clinical outcome.
"OPuS-1 represents a milestone study in establishing the proof of concept that prophylaxis with an oral kallikrein inhibitor can effectively reduce attacks for patients living with HAE," said
"The efficacy and safety profile of BCX4161 seen in the OPuS-1 trial strongly support its continued development," said Dr.
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Discovered by BioCryst, BCX4161 is a novel, selective inhibitor of plasma kallikrein in development for prevention of attacks in patients with hereditary angioedema (HAE). By inhibiting plasma kallikrein, BCX4161 suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients.
About Hereditary Angioedema
HAE is a rare, severely debilitating and potentially fatal genetic condition that occurs in about 1 in 10,000 to 1 in 50,000 people. HAE symptoms include recurrent episodes of edema in various locations, including the hands, feet, face, genitalia and airway. In addition, patients often have bouts of excruciating abdominal pain, nausea and vomiting that are caused by swelling in the intestinal wall. Airway swelling is particularly dangerous and can lead to death by asphyxiation. Further information regarding HAE can be found at www.haea.org.
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