BioCryst Pharmaceuticals, Inc. has completed enrollment in OPuS-2 (Oral ProphylaxiS-2), a blinded, randomized, placebo-controlled clinical trial of orally-administered avoralstat in patients with HAE.
OPuS-2 is a 12-week, three-arm, parallel cohort trial designed to evaluate the efficacy and safety of two doses of avoralstat, 300 mg and 500 mg, administered three-times daily compared with placebo. This trial is being conducted in the U.S., Canada and Europe. The primary efficacy endpoint for the trial is the mean angioedema attack rate, which will be reported for each avoralstat dose group compared to placebo.
Final patient visits will occur in January 2016; therefore, BioCryst expects to report OPuS-2 results in early 2016. The results of this trial will be provided for regulatory discussions intended to determine the scope of any additional information that may be required for completion of avoralstat registration.
BioCryst has been corresponding with regulatory agencies regarding deferral of a two-year rat carcinogenicity study for avoralstat. The results from this type of study are normally required to be available at the time of submission for approval. Currently, BioCryst has agreement with the European Medicines Agency (EMA) regarding its request to defer submission of results as a post-filing commitment. Agreement has not been reached with the U.S. Food and Drug Administration (FDA) regarding a deferral at this time. At the end-of-Phase 2 meeting following the completion of OPuS-2, BioCryst will engage in further dialogue with the FDA to discuss deferral, in the context of all available toxicology and clinical data. BioCryst plan to initiate a rat carcinogenicity study in early 2016. Without a deferral, the NDA filing would occur in 2018.
Discovered by BioCryst, avoralstat is a novel, selective inhibitor of plasma kallikrein in development for prevention of attacks in patients with HAE. By inhibiting plasma kallikrein, avoralstat suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients.