BACKGROUND Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) is a new avenue for treating migraine. The efficacy and safety of intravenous Lu AG09222, a humanized monoclonal antibody directed against the PACAP ligand, for migraine prevention are unclear. METHODS In a phase 2, double-blind, randomized, placebo-controlled trial, we enrolled adult participants (18 to 65 years of age) with migraine for whom two to four previous preventive treatments had failed to provide a benefit. The trial included a 4-week treatment period and an 8-week follow-up period. Participants were randomly assigned in a 2:1:2 ratio to receive a single-dose baseline infusion of 750 mg of Lu AG09222, 100 mg of Lu AG09222, or placebo. The primary end point was the mean change from baseline in the number of migraine days per month, during weeks 1 through 4, in the Lu AG09222 750-mg group as compared with the placebo group. RESULTS Of 237 participants enrolled, 97 received 750 mg of Lu AG09222, 46 received 100 mg of Lu AG09222, and 94 received placebo. The mean number of baseline migraine days per month was 16.7 in the overall population, and the mean change from baseline over weeks 1 through 4 was -6.2 days in the Lu AG09222 750-mg group, as compared with -4.2 days in the placebo group (difference, -2.0 days; 95% confidence interval, -3.8 to -0.3; P = 0.02). Adverse events with a higher incidence in the Lu AG09222 750-mg group than in the placebo group during the 12-week observation period included coronavirus disease 2019 (7% vs. 3%), nasopharyngitis (7% vs. 4%), and fatigue (5% vs. 1%). CONCLUSIONS In a phase 2 trial, a single intravenous infusion of 750 mg of Lu AG09222 showed superiority over placebo in reducing migraine frequency over the subsequent 4 weeks. (Funded by H. Lundbeck; HOPE ClinicalTrials.gov number, NCT05133323.).

中文翻译：

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用于预防偏头痛的 PACAP 单克隆抗体。


背景 靶向垂体腺苷酸环化酶激活多肽 （PACAP） 是治疗偏头痛的新途径。静脉注射 Lu AG09222（一种针对 PACAP 配体的人源化单克隆抗体）预防偏头痛的有效性和安全性尚不清楚。方法 在一项 2 期、双盲、随机、安慰剂对照试验中，我们招募了患有偏头痛的成年参与者 （18 至 65 岁），他们之前的 2 至 4 次预防性治疗未能带来益处。该试验包括 4 周的治疗期和 8 周的随访期。参与者以 2：1：2 的比例随机分配接受 750 mg Lu AG09222、100 mg Lu AG09222 或安慰剂的单剂量基线输注。主要终点是与安慰剂组相比，Lu AG09222 750 mg 组第 1 周至第 4 周每月偏头痛天数相对于基线的平均变化。结果在入组的 237 名参与者中，97 名接受了 750 mg 的 Lu AG09222,46 名接受了 100 mg 的 Lu AG09222,94 名接受了安慰剂。总体人群每月基线偏头痛的平均天数为 16.7 天，Lu AG09222 750 mg 组第 1 周至第 4 周从基线的平均变化为 -6.2 天，而安慰剂组为 -4.2 天（差异，-2.0 天;95% 置信区间，-3.8 至 -0.3;P = 0.02）。在 12 周的观察期内，Lu AG09222 750 mg 组发生率高于安慰剂组的不良事件包括 2019 冠状病毒病 （7% vs. 3%）、鼻咽炎 （7% vs. 4%） 和疲劳 （5% vs. 1%）。结论 在一项 2 期试验中，单次静脉输注 750 mg Lu AG09222 在随后 4 周内降低偏头痛频率方面优于安慰剂。（由 H. 灵北;HOPE ClinicalTrials.gov 号，NCT05133323.）。