BioCryst Pharmaceuticals Inc., announced preliminary results from its OPuS-1 (Oral ProphylaxiS-1) proof of concept Phase 2a clinical trial of orally-administered BCX4161 in patients with hereditary angioedema (HAE). The trial met the primary efficacy endpoint, several secondary endpoints and all other objectives established for the trial.
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%.
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 Marcus Maurer, professor of Dermatology and Allergy, Charité-Universitäsmedizin, Berlin, and the principal investigator for the study. “Existing therapies for prophylaxis of attacks in patients with HAE require frequent i.v. infusions, or the use of oral androgens that have significant long term side effects. The OPuS-1 results open up the possibility of an exciting new treatment option for this challenging disease.”
“The efficacy and safety profile of BCX4161 seen in the OPuS-1 trial strongly support its continued development,” said Dr. William Sheridan, chief medical officer at BioCryst. “We look forward to working with clinical investigators, the HAE community and regulatory authorities in advancing BCX4161 to the next stage and starting the OPuS-2, 12-week trial later this year.”
Date: May 27, 2014
Source: BioCryst Pharmaceuticals