BioCryst Reports Positive Initial Results in Acute HAE Trial

Rare Daily Staff

BioCryst Pharmaceuticals said initial results of a clinical study of its experimental drug BXC7353 showed it was superior to a placebo for the majority of efficacy endpoints in hereditary angioedema (HAE) patients suffering an acute attack.

HAE is a rare, genetic disorder that results in recurring attacks of swelling in various parts of the body, including the abdomen, face, feet, genitals, hands and throat that can be can debilitating and painful. Attacks that obstruct the airways are potentially life-threatening due to the risk of asphyxiation.

BCX7353 is a novel oral plasma kallikrein inhibitor being developed for both prophylactic and acute treatment of HAE attacks. Kallikrein is an enzyme that is chronically uncontrolled in people with HAE, to help prevent attacks.

The study, known as ZENITH-1, was designed as an exploratory trial to determine if BCX7353 showed a clinically meaningful benefit on any of several different efficacy endpoints evaluating HAE attack symptom severity. The data will be used to design a phase 3 registration trial, to identify the dose or doses the company could advance, and to assess safety and tolerability.

Adults with HAE type I or II self-administered a dose of blinded study drug for three attacks; two treated with active drug and one with placebo, in a randomized sequence. Subjects were asked to administer blinded study medicine within one hour of onset of symptoms. Subjects were free to use approved prescribed acute medications but were asked to wait at least four hours post-study drug if possible. Patient completed trial diaries to collect information on symptoms, subjective scale and use of standard-of-care medicines prior to dosing and at 1, 2, 3, 4, 8 and 24 hours after study drug administration.

In the 750 mg dose cohort of the trial, which has completed, 33 patients treated a total of 95 attacks (64 with BCX7353, 31 with placebo). Patients self-treated their HAE attacks on a blinded basis with oral BCX7353 or oral placebo and recorded their symptoms and attack severity using both a subjective scale and a standardized questionnaire. Patients also recorded the time they used any standard-of-care acute treatment medicine. BCX7353 was superior to placebo for multiple clinical outcomes.

“We are thrilled to see such a robust treatment effect with BCX7353 in ZENITH-1, using a modern approach with self-administered therapy. We were able to demonstrate clinically important treatment effects very early after oral dosing, which lasted through 24 hours,” said William Sheridan, chief medical officer of BioCryst.

Results from the ongoing evaluation of the 250 mg and 500 mg dose levels of oral BCX7353 in ZENITH-1 are expected in the first quarter of 2019.

Compared to placebo, improvement in symptoms and subjective scores was seen as early as one hour after oral BCX7353 dosing and was sustained through 24 hours. Through 24 hours, standard-of-care medication use was reduced by 31.6 percent after BCX7353 compared with placebo, and no or mild symptoms were reported in 64.1 percent of attacks treated with BCX7353 compared with 32.3 percent of attacks treated with placebo.

BCX7353 was generally safe and well tolerated. No serious adverse events were reported in patients receiving BCX7353. The most commonly reported adverse events were cold-like symptoms, diarrhea, and headache. Two patients discontinued the study. One stopped after a transient, localized rash developed following a dose of BCX7353. The other patient discontinued following a placebo dose due to abdominal pain.

“ZENITH-1 represents a groundbreaking study, as the first clinical trial to demonstrate effective treatment of acute HAE attacks with an oral therapy,” said Hilary Longhurst, honorary consultant immunologist, Addenbrookes Hospital, Cambridge, United Kingdom, and principal investigator of the ZENITH-1 trial. “The observed effect of BCX7353 within one hour of dosing and the substantial reduction in rescue medication use compared to placebo suggest that BCX7353 has outstanding potential to offer physicians and patients an urgently needed new oral therapy option.”

September 4, 2018
Photo: William Sheridan, chief medical officer of BioCryst