Potential Oral Therapy, BCX7353, Seen in Phase 3 Trial to Markedly Reduce HAE Attacks

Potential Oral Therapy, BCX7353, Seen in Phase 3 Trial to Markedly Reduce HAE Attacks

Daily treatment with BCX735, an investigative oral inhibitor of plasma kallikrein by BioCryst Pharmaceuticals, was well-tolerated and lowered attack rates in hereditary angioedema (HAE) patients included in a Phase 3 trial.

Both 110 mg and 150 mg doses provided a significant benefit by decreasing HAE attacks — the APeX-2 trial’s primary efficacy goal — by 30% and 44%, respectively, compared to placebo. The 150 mg dose also led to a 70% or greater reduction from baseline (the study’s start) in attack rates in 50% of the patients, compared to 15% of people given a placebo.

Also compared to placebo, the treatment’s higher dose resulted in a 66% reduction in HAE attacks in patients with less than two attacks per month at baseline, and in a 40% reduction in those with two or more monthly attacks.

Bose doses were generally safe and well-tolerated, and no treatment-related serious side effects were reported. The most frequent therapy-related adverse events were nausea, indigestion, and diarrhea.

Based on these results, BioCryst is planning to submit a new drug application to the U.S. Food and Drug Administration (FDA) toward the end of this year, and a marketing authorization application to the European Medicines Agency (EMA) in the first quarter of 2020.

BCX7353 is a selective inhibitor of plasma kallikrein, a precursor of the inflammatory molecule bradykinin. HAE patients have excessive levels of bradykinin, leading to angioedema attacks and pain. The potential treatment is being developed as a liquid for acute treatment of HAE, and as a capsule to prevent attacks.

The double-blind trial (NCT03485911) includes 121 type 1 or 2 patients in the U.S., Canada, and Europe, and is testing the two doses of BCX7353. Forty-one patients received the lower 110 mg dose, 40 the higher 150 mg dose, and 40 more were on placebo.

All 108 patients who completed 24 weeks of treatment continued into the ongoing 48-week extension phase, where those previously on placebo are now getting one of the therapy’s two doses. People who complete these 48 weeks may continue on BCX7353 for up to 96 weeks. BioCryst is also conducting a long-term and open-label Phase 2/3 safety trial called APeX-S (NCT03472040).

Mentioning the unmet need for a “cost-effective, convenient, oral therapy to manage” HAE, Jon Stonehouse, BioCryst’s CEO, said in a press release that the results of the 150 mg dose make BCX7353 “a new oral therapy that patients will want to try.”

“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,” he added.

The company is also planning to submit APeX-2 trial findings for peer‑reviewed publication and to present them and at a scientific meeting.

Prior results of the Phase 2 APeX-1 trial (NCT02870972) showed that prophylactic treatment with 125 mg of BCX7353 lowered HAE attacks by more than 70% compared to placebo. A greater number of patients also remained attack-free.

In turn, the ZENITH-1 Phase 2 study (NCT03240133) reported that BCX7353 eased HAE attacks, the occurrence of symptoms, and the use of rescue medications.

“The additional clinical information we now have from APeX-2 confirms that [BCX7353] is effective at preventing HAE attacks in a large segment of the HAE patient population while having a very attractive tolerability profile,” said Bruce Zuraw, MD, principal investigator of the APeX-2 trial.

“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,” added Zuraw, who is  chief of the Division of Rheumatology, Allergy and Immunology at the University of California School of Medicine.

The company recently held a conference call and webcast on APeX-2 findings. The webcast and slides are available here. A replay of the call is also available, more details here.

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