Background

Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.

Objective

Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).

Methods

APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period.

Results

A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred.

Conclusion

Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.

中文翻译：

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每日一次口服贝罗司他预防遗传性血管性水肿发作：一项随机、双盲、安慰剂对照的 3 期试验

背景

Berotralstat (BCX7353) 是一种口服、每日一次的血浆激肽释放酶抑制剂，正在开发用于预防遗传性血管性水肿 (HAE) 发作。

客观的

我们的目标是确定 berotralstat 在 24 周治疗期内（APeX-2 3 期试验）对 HAE 患者的疗效、安全性和耐受性。

方法

APeX-2 是一项双盲、平行组研究，该研究将 11 个国家/地区 40 个地点的患者以 1:1:1 的比例随机分配接受每日一次 110 毫克或 150 毫克的贝罗司他或安慰剂（Clinicaltrials.gov 标识符 NCT03485911 ）。年龄在 12 岁或以上的因 C1 抑制剂缺乏而患有 HAE 且在预期磨合期的前 56 天内至少有 2 次研究者确认的 HAE 发作的患者符合条件。主要疗效终点是 24 周治疗期间研究者确认的 HAE 发作率。

结果

共有 121 名患者被随机分组​​；其中 120 人接受了至少 1 剂研究药物（在 110-mg 剂量 berotralstat、150-mg 剂量 berotralstat 和安慰剂组中，n = 41、40 和 39）。 与安慰剂（每月 2.35 次发作）相比， Berotralstat在 110 毫克（每月 1.65 次发作；P = .024）和 150 毫克（每月 1.31 次发作；P < .001）时的发作率均显着降低。与安慰剂相比，贝罗司他发生的最常见的治疗出现的不良事件是腹痛、呕吐、腹泻和背痛。没有发生与药物相关的严重治疗出现的不良事件。

结论

与安慰剂相比，110 毫克和 150 毫克剂量的贝罗司他均降低了 HAE 发作率，并且安全且耐受性良好。在每天 150 毫克的剂量下观察到最有利的获益风险分布。