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avoralstat & next generation kallikrein inhibitors for HAE


Structure of PNP enzyme

May 16 is HAE awareness day

Avoralstat is being developed as an oral prophylactic treatment for patients suffering from Hereditary Angioedema (HAE). Avoralstat inhibits plasma kallikrein and suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients.

In May 2014 BioCryst, announced that the OPuS-1 (Oral ProphylaxiS-1) Phase 2a proof of concept clinical trial met its primary efficacy endpoint, several secondary endpoints and all other objectives established for the trial. OpuS-1 enrolled 24 HAE patients with a history of HAE attack frequency of at least 1 per week. Treatment with avoralstat demonstrated a statistically significant mean attack rate reduction of 0.45 attacks per week versus placebo, p<0.001. The mean attack rate per week was 0.82 on BCX4161 treatment, compared to 1.27 on placebo.

In December 2014, BioCryst initiated enrollment in OPuS-2 (Oral ProphylaxiS-2). OPuS-2 was a blinded, randomized, 12-week, three-arm, parallel cohort design trial evaluated the efficacy and safety of two different dose regimens of avoralstat administered three-times daily, 300 mg and 500 mg, compared with placebo. The primary efficacy endpoint of the trial was the mean angioedema attack rate, reported for each avoralstat dose group compared to placebo. The trial was conducted in the U.S., Canada and Europe. On February 8, 2016, we announced that treatment with 500 mg & 300 mg of avoralstat three times daily failed to demonstrate a statistically significantly lower mean attack rate versus placebo.

BCX7353 and other 2nd Gen kallikrein inbitors

BioCryst’s goals for its second-generation kallikrein inhibitor program are to develop and launch a revolutionary treatment for hereditary angioedema patients, consisting of an oral, once-a-day drug that could restore the normal phenotype of kallikrein inhibition – resulting in elimination of angioedema attacks.

In October 2015, BioCryst announced that it’s randomized, placebo-controlled, Phase 1 clinical trial of orally-administered BCX7353 in healthy volunteers successfully met all of its objectives. BCX7353 was generally safe and well tolerated at all doses up to 500 mg once-daily for 7 days and 350 mg once-daily for 14 days in healthy volunteers, with dose-related drug exposure and a half-life supporting a once-daily dosing regimen. There were no serious adverse events (AEs) and most AEs were mild. No dose-limiting toxicity was identified.

The safety, tolerability, drug exposure and on-target plasma kallikrein inhibition results strongly support advancing the development program into a Phase 2 study in hereditary angioedema (HAE) patients. APeX-1, a Phase 2 trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of BCX7353 as a preventative treatment to reduce the frequency of attacks in HAE patients is expected report results before the end of 2016.


For more information on hereditary angioedema, please visit the following websites: