BioCryst Pharmaceuticals, Inc. presents data showing that an oral formulation of BCX7353 was rapidly absorbed and exhibited a long half-life, two important characteristics of desired new acute treatments for HAE attacks.
In the trial, the pharmacokinetic (PK) and kallikrein inhibition profiles of BCX7353 were evaluated for 24 hours post-dose in six subjects with HAE Type I or II who were given a single 750 mg oral dose of BCX7353 in a period between HAE attacks.
The target concentration of BCX7353 that restores plasma kallikrein suppression to normal, or above-normal, levels is ≥ 8x EC50. In the trial, mean concentrations of BCX7353 were approximately 16x EC50 within 30 min, and remained at or above this level through at least 24 hours post-dose.
“Both rapid onset of action and sustained duration of activity are critical attributes that patients and physicians seek in an improved single-dose oral option for the acute treatment of HAE attacks,” said Dr. William Sheridan, Chief Medical Officer of BioCryst.
“This PK profile supports the clinical benefits that we saw in the placebo-controlled ZENITH-1 clinical trial of a single 750 mg dose of BCX7353 to treat HAE attacks,” Sheridan added.
In order to evaluate prevention of attack progression and symptom relief in the ZENITH-1 trial, study drug (BCX7353 or placebo) was administered early (mean time of administration was 35 minutes) after the onset of symptoms of angioedema, when baseline mean composite visual analog scale (VAS) scores were 14 to 15, on a scale of 0-100.
In ZENITH-1, the VAS scores of subjects receiving a single dose of BCX7353 750 mg were reduced by 6.98 points (p=0.0024) compared to placebo by four hours post-dose, and, through 24 hours, use of standard of care medication to treat HAE attacks was reduced by 31.6 percent after treatment with BCX7353 compared to treatment with placebo (p=0.0029). BCX7353 750 mg single doses were generally safe and well tolerated.