BioCryst’s Oral Drug Meets Primary Endpoint in Phase 3

BioCryst Pharmaceuticals, Inc. recently announced that the randomized (n=121), double-blind, placebo-controlled, Phase 3 APeX-2 trial of once-daily, oral BCX7353 for the prevention of hereditary angioedema (HAE) attacks 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% reduction in their HAE attack rate compared to baseline, compared to 15% 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% 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% (p=0.005).

Of 108 patients who completed 24 weeks of study drug treatment, 100% 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 5% 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% reduction in attack rate, we have a new oral therapy that patients will want to try,” said Jon Stonehouse, Chief Executive Officer of BioCryst. “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.”

The results from APeX-2 support the submission of a new drug application (NDA) to the US 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, MD, 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.

APeX-2 is a randomized, double-blind, placebo-controlled, three-arm trial testing two dose levels of orally administered once-daily BCX7353 (110 mg and 150 mg) for prevention of angioedema attacks. The trial enrolled 121 patients with Type I and II HAE in the United States, Canada and Europe.

The primary efficacy endpoint of APeX-2 is the rate of investigator confirmed angioedema attacks over 24 weeks of study drug administration. Following study qualification during a run-in period of 14 to 56 days, patients were randomized 1:1:1 to receive placebo or one of the two doses of BCX7353. Randomization was stratified on a baseline attack rate of <2/month or ≥2/month. Forty-one patients were randomized to 110 mg BCX7353, 40 to 150 mg BCX7353, and 40 to placebo. There was a clear dose response, with the 110-mg dose of BCX7353 reducing HAE attack rate by 30% (p=0.024) compared to placebo. As noted above, the 150-mg dose reduced attack rate by 44% (p<0.001) compared to placebo.

To qualify for the trial, patients were required to have a specified number of investigator-confirmed HAE attacks during the run-in period of a maximum of 56 days from the screening visit. The average baseline attack rate prior to randomization was 3.0 per 28 days.

Following completion of the 24-week analysis period, patients continued on study drug in an ongoing extension phase of APeX-2 through 48 weeks. Patients randomized to placebo for 24 weeks were re-randomized to receive one of the two doses of study drug in the extension phase of the trial. Patients who complete 48 weeks may continue in the trial on open-label BCX7353 for up to 96 weeks.

Discovered by BioCryst, BCX7353 is a novel, oral, once-daily, selective inhibitor of plasma kallikrein currently in advanced clinical development for the prevention and treatment of angioedema attacks in patients with HAE. BCX7353 was generally safe and well tolerated in the Phase 3 APeX-2 and Phase 2 APeX-1 clinical trials. In APeX-2, BCX7353 (150 mg) reduced the HAE attack rate by 44% (p<0.001) compared to placebo, and reduced the HAE attack rate by ≥ 70% in 50% of patients. BioCryst is currently conducting APeX-S, a long-term safety clinical trial, and plans to submit an NDA to the FDA in the fourth quarter of 2019 and an MAA to the EMA in the first quarter of 2020. BioCryst has also completed the ZENITH-1 clinical trial. ZENITH-1 was a proof-of-concept Phase 2 clinical trial testing oral BCX7353 for the treatment of acute angioedema attacks.

BioCryst discovers novel, oral small-molecule medicines that treat rare diseases in which significant unmet medical needs exist and an enzyme plays a key role in the biological pathway of the disease. BioCryst has several ongoing development programs including BCX7353, an oral treatment for hereditary angioedema; BCX9930, an oral Factor D inhibitor for the treatment of complement-mediated diseases; galidesivir, a potential treatment for Marburg virus disease and Yellow Fever, and a preclinical program to develop oral ALK-2 inhibitors for the treatment of fibrodysplasia ossificans progressiva. RAPIVAB (peramivir injection), a viral neuraminidase inhibitor for the treatment of influenza, is BioCryst’s first approved product and has received regulatory approval in the US, Canada, Australia, Japan, Taiwan, Korea, and the European Union. Post-marketing commitments for RAPIVAB are ongoing. For more information, visit www.BioCryst.com.