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.
"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.
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.
As a part of BioCryst's strategy to become a leader in the treatment of HAE, we are finalizing our evaluation of multiple potent and specific second generation oral kallikrein inhibitors. Oral bioavailability of these compounds ranges between 20% and 60% in animals. One or more candidates are expected to enter preclinical development by the end of 2013.
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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.
This press release contains forward-looking statements, including
statements regarding future results, performance or achievements. These
statements involve known and unknown risks, uncertainties and other
factors which may cause BioCryst's actual results, performance or
achievements to be materially different from any future results,
performances or achievements expressed or implied by the forward-looking
statements. These statements reflect our current views with respect to
future events and are based on assumptions and subject to risks and
uncertainties. Given these uncertainties, you should not place undue
reliance on these forward-looking statements. Some of the factors that
could affect the forward-looking statements contained herein include:
that BioCryst may not be able to enroll the required number of subjects
in the Phase 2a clinical trial of BCX4161; that the Phase 2a trial of
BCX4161 may not have a favorable outcome or may not be successfully
completed; that the
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