BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) today announced that the randomized, placebo-controlled, Phase 1 clinical trial of orally-administered BCX4161 in healthy volunteers successfully met all of its objectives. The safety, tolerability, drug exposure and on-target kallikrein inhibition results of this Phase 1 trial strongly support advancing the development program into a Phase 2a study in hereditary angioedema (HAE) patients.
Overall, 87 healthy volunteers completed the study; 30 received a single dose of BCX4161 from 50 mg up to 1000 mg, 40 subjects received 100 mg, 200 mg, 400 mg, or 800 mg BCX4161 every eight hours for seven days and 17 received placebo.
Oral administration of BCX4161 was generally safe and well tolerated. There were no serious adverse events and no dose limiting adverse events. Laboratory tests of coagulation remained normal. Drug exposure was dose proportional through 400 mg three times a day. Steady state (day seven) blood levels were 30% higher compared to the first day of dosing. At 400 mg three times a day, pre-dose geometric mean (coefficient of variance, CV) drug levels on day 7 were 28.6 ng/mL (CV 77%) and post-dose maximum drug levels were 152 ng/mL (CV 57%). Kallikrein inhibition was observed throughout the dosing interval, p<0.0001 compared to placebo.
“We are very pleased that this first-in-human trial of BCX4161 met all of its objectives. The safety, tolerability, level and consistency of drug exposure and kallikrein inhibition achieved significantly increases our confidence to move this program forward,” said Dr. William P. Sheridan, Chief Medical Officer at BioCryst. “We look forward to conducting a Phase 2 proof of concept study later this year to evaluate BCX4161’s ability to reduce the frequency of edema attacks in HAE patients.”“The successful development of an oral kallikrein inhibitor such as BCX4161 for the prevention of HAE attacks is an exciting advance that has significant implications for HAE treatment,” said Dr. Bruce Zuraw, M.D., Professor, University of California, San Diego and Staff Physician at the V.A. Medical Center, San Diego. “If BCX4161 fulfills the promise shown in this study, it will provide a more effective alternative to androgens, currently the mainstay of oral HAE treatment, with substantially less side effects. BCX4161 has the potential to be an important new treatment for optimally managing patients with HAE.” The Phase 2a clinical trial in patients with HAE is expected to begin in the fourth quarter of 2013. This trial will test 400 mg of BCX4161 administered three times daily for 28 days in a randomized, placebo-controlled, two-period cross-over design. Approximately 25 HAE patients who have a high frequency of attacks (≥ 1 per week) will be enrolled. The main goals for this clinical trial are to evaluate the safety and tolerability of BCX4161 and to estimate the degree of efficacy in reducing the frequency of attacks. This study is designed to provide proof of concept for oral kallikrein inhibition as a treatment strategy for hereditary angioedema.