The randomized (n=121), double-blind, placebo-controlled, Phase 3 APeX-2 trial of once-daily, oral BCX7353 for the prevention of HAE attacks has achieved its primary endpoint for both dose levels (110 mg and 150 mg), with the 150 mg dose reducing the attack rate in HAE patients by 44 percent (p<0.001) compared to placebo.
Fifty percent of patients receiving 150 mg BCX7353 in APeX-2 had a ≥ 70 percent reduction in their HAE attack rate compared to baseline, compared to 15 percent of placebo patients (p=0.002).
In patients on the 150 mg dose with a baseline attack rate of < 2 attacks per month, BCX7353 reduced the HAE attack rate by 66 percent compared to placebo (p=0.009). In patients with a baseline attack rate of ≥ 2 attacks per month, the attack rate was reduced by 40 percent (p=0.005).
Of 108 patients who completed 24 weeks of study drug treatment, 100 percent continued into the ongoing 48 week extension phase of the trial.
In APeX-2, both the 110 mg and 150 mg dose levels of once-daily oral BCX7353 were generally safe and well-tolerated. No drug-related serious adverse events were reported.
The most common drug-related adverse events reported in at least five percent of patients in APeX-2 were: nausea (9.8% 110 mg, 7.5% 150 mg, 15.4% placebo), dyspepsia (9.8% 110 mg, 7.5% 150 mg, 5.1% placebo) and diarrhea (7.3% 110 mg, 10% 150 mg, 0% placebo).
“HAE patients around the world desperately want access to a cost-effective, convenient, oral therapy to manage their disease. Given the profile of the 150 mg dose of BCX7353 in APeX-2, with half of patients experiencing at least a 70 percent reduction in attack rate, we have a new oral therapy that patients will want to try,” said Jon Stonehouse, CEO of BioCryst Pharmaceuticals, Inc.
“With successful results from APeX-2, BioCryst is committed to making it easy for HAE patients around the world to access this potentially life-changing oral therapy, and we believe BCX7353 is positioned to become a front-line therapy option,” Stonehouse added.
The results from APeX-2 support the submission of a new drug application (NDA) to the U.S. Food and Drug Administration (FDA). BioCryst plans to submit an NDA to the FDA in the fourth quarter of 2019 and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the first quarter of 2020.
“The additional clinical information we now have from APeX-2 confirms that this is an oral kallikrein inhibitor that is effective at preventing HAE attacks in a large segment of the HAE patient population while having a very attractive tolerability profile. Based on this profile, and the consistent observation that real-world efficacy has been higher than clinical trial efficacy with HAE therapies, I expect many patients will want to try this oral option to see how well it works for them,” said Bruce Zuraw, M.D., professor of medicine and chief of the Division of Rheumatology, Allergy and Immunology at the University of California School of Medicine, and principal investigator of the APeX-2 trial.
The company plans to submit detailed results from the APeX-2 trial for peer‑reviewed publication and presentation.