SAFETY AND EFFICACY OF OBICETRAPIB IN PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

IF 5.9 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

American journal of preventive cardiology Pub Date : 2025-09-01 DOI:10.1016/j.ajpc.2025.101131

Andy Hsieh PharmD , Stephen Nicholls MBBS PhD , Adam J Nelson MBBS PhD , Marc Ditmarsch MD , John J.P. Kastelein MD, PhD , Christie M. Ballantyne MD , Kausik K. Ray MD, MPHil, FMedSc , Ann Marie Navar MD, PhD , Steven E. Nissen MD , Anne C. Goldberg MD , Liam R. Brunham MD, PhD , Erin Wuerdeman , Annie Neild , Douglas Kling , Brian A. Ference MD, MPHIL, MSC , Ulrich Laufs MD , Maciej Banach MD , Roxana Mehran MD , Alberico L. Catapano , Michael H. Davidson MD

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Abstract

Therapeutic Area

Pharmacologic Therapy

Background

BROOKLYN examined the efficacy, safety, and tolerability of obicetrapib 10 mg, as an adjunct to maximally tolerated lipid-modifying therapies, in patients with heterozygous familial hypercholesterolemia (HeFH) and suboptimal LDL-C control.

Methods

This was a phase 3, randomized, double-blind, placebo-controlled trial NCT05425745 with 1 year follow up in 354 patients across 70 sites. Participants (n=354) with HeFH and fasting LDL-C ³70 mg/dL taking maximally tolerated lipid-modifying therapies were randomly assigned to receive obicetrapib 10 mg or matching placebo orally daily for 52 weeks in a 2:1 ratio. Study primary endpoint assessed obicetrapib compared with placebo in LS mean percent change from baseline to week 12 in LDL-C. Secondary endpoints included obicetrapib compared with placebo in percent changes from baseline in Apo B, nonHDL-C, HDL-C, total-C, Lp(a), and TG, and safety measures; Apo A1 was an exploratory endpoint.

Results

Mean baseline lipoprotein lipid levels for obicetrapib and placebo, respectively, were LDL-C: 123.4 and 119.9 mg/dL; ApoB: 107.2 and 105.3 mg/dL; non-HDL-C: 148.4 and 146.7 mg/dL; and HDL-C: 53.2 and 50.2 mg/dL. Obicetrapib, compared with placebo, significantly reduced mean LDL-C -36.3% at day 84 (P<0.0001) and -41.5% at day 365 (P<0.0001). On day 84 and day 365, obicetrapib, compared with placebo, significantly reduced mean ApoB -24.4%, -25.8%; non-HDL-C -34.5%, -37.5%; Lp(a) -45.9%, -54.3%; and increased HDL-C 138.7%,121.4%, respectively. Obicetrapib was well tolerated with no serious adverse events or clinically significant changes in vital signs, electrocardiograms, or other clinical laboratory values.

Conclusions

Obicetrapib, as an adjunct to maximally tolerated lipid-modifying therapies, produced significant LDL-C lowering at day 84 with sustained effect through day 365 in patients with HeFH. Obicetrapib holds promise for patients with HeFH who are unable to attain their LDL-C treatment targets with available lipid-lowering agents.

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obicetrapib治疗杂合子家族性高胆固醇血症的安全性和有效性

治疗领域：药物治疗背景：brooklyn研究了obicetrapib 10mg在杂合子家族性高胆固醇血症（HeFH）和LDL-C控制不佳的患者中作为最大耐受性脂质修饰疗法的辅助疗法的有效性、安全性和耐受性。方法：这是一项3期、随机、双盲、安慰剂对照试验NCT05425745，在70个地点的354名患者中进行了1年的随访。HeFH和空腹LDL-C³70 mg/dL的参与者（n=354）接受最大耐受的脂质修饰治疗，随机分配以2:1的比例每天口服obicetrapib 10 mg或匹配的安慰剂，持续52周。研究的主要终点评估了obicetrapib与安慰剂相比，从基线到第12周LDL-C的LS平均百分比变化。次要终点包括与安慰剂相比，奥比西拉比与基线相比Apo B、非HDL-C、HDL-C、总c、Lp(a)和TG的百分比变化，以及安全性措施；载脂蛋白A1是一个探索性终点。结果：奥比西拉比和安慰剂组的平均基线脂蛋白脂水平分别为：LDL-C: 123.4和119.9 mg/dL；载脂蛋白：107.2和105.3 mg/dL；非hdl - c: 148.4和146.7 mg/dL；HDL-C: 53.2和50.2 mg/dL。与安慰剂相比，Obicetrapib在第84天显著降低平均LDL-C -36.3% (P<0.0001)，在第365天显著降低-41.5% （P<0.0001）。在第84天和第365天，与安慰剂相比，obicetrapib显着降低了平均ApoB -24.4%, -25.8%；非hdl - c -34.5%, -37.5%；Lp(a) -45.9%, -54.3%；HDL-C分别升高138.7%、121.4%。Obicetrapib耐受性良好，没有严重的不良事件或生命体征、心电图或其他临床实验室值的临床显著变化。结论sobicetrapib作为最大耐受的脂质调节疗法的辅助疗法，在HeFH患者的第84天显著降低LDL-C，并持续到365天。Obicetrapib对于无法通过现有降脂药物达到LDL-C治疗目标的HeFH患者具有希望。

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