Initial results from ZENITH-1 trial of BCX 7353 or both prophylactic and acute treatment of HAE attacks.- BioCryst Pharma.

BioCryst Pharmaceuticals, Inc., announced initial results from the ZENITH-1 trial showing that a single 750 mg oral dose of BCX 7353 was well tolerated and superior to placebo (p<0.05) against the majority of efficacy endpoints evaluated in hae patients suffering an acute attack. bcx7 353 is a novel oral plasma kallikrein inhibitor being developed for both prophylactic and acute treatment of hae attacks>

In order to guide selection of dose and endpoints for a potential future registration trial for the acute treatment of HAE attacks, ZENITH-1 was designed as an exploratory trial to determine if BCX 7353 showed a clinically meaningful benefit on any of several different efficacy endpoints evaluating HAE attack symptom severity. In the 750 mg dose cohort of the trial, which has completed, 33 patients treated a total of 95 attacks (64 with BCX 7353, 31 with placebo). Patients self-treated their HAE attacks on a blinded basis with oral BCX 7353 or oral placebo and recorded their symptoms and attack severity using both a Visual Analog Scale (VAS) and a standardized questionnaire. Patients also recorded the time they used any standard-of-care (SOC) acute treatment medicine. BCX 7353 was superior to placebo for multiple clinical outcomes.Importantly, compared to placebo, improvement in symptoms and VAS scores was seen as early as one hour after oral BCX 7353 dosing, and was sustained through 24 hours. Through 24 hours, SOC medication use was reduced by 31.6 percent after BCX 7353 compared with placebo (p=0.0029), and no or mild symptoms were reported in 64.1 percent of attacks treated with BCX 7353 compared with 32.3 percent of attacks treated with placebo (p=0.0038). These and the other clinically meaningful results from ZENITH-1 highlight an attractive profile for patients seeking an oral treatment for acute HAE attacks.

In the ZENITH-1 trial, oral BCX 7353 750 mg was generally safe and well tolerated. No serious adverse events were reported in patients receiving BCX 7353. There were no grade 3 or 4 adverse events, and no grade 2, 3 or 4 laboratory abnormalities. The most commonly reported adverse events were nasopharyngitis (4/64 attacks treated with BCX 7353 vs 1/31 for placebo), diarrhea (3/64 with BCX 7353 vs 0/31 for placebo) and headache (3/64 with BCX 7353 vs 0/31 for placebo). There were two discontinuations in the trial. One patient discontinued following a BCX 7353 dose due to a transient, localized rash and one patient discontinued following a placebo dose due to abdominal pain.

Comment:Results from the ongoing evaluation of the 250 mg and 500 mg dose levels of oral BCX 7353 in ZENITH-1 are expected in the first quarter of 2019.