泰尼雅和卢塞恩：贝伐珠单抗生物类似药 faricimab 在湿性年龄相关性黄斑变性 2 年治疗和延长给药的 3 期临床试验的 2 年结果。

TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2.

机构信息

Sierra Eye Associates and the University of Nevada, Reno, School of Medicine, Reno, Nevada.

Roche Products, Ltd., Welwyn Garden City, United Kingdom.

出版信息

Ophthalmology. 2024 Aug;131(8):914-926. doi: 10.1016/j.ophtha.2024.02.014. Epub 2024 Feb 19.

DOI:10.1016/j.ophtha.2024.02.014

PMID:38382813

Abstract

PURPOSE

To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A.

DESIGN

TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials.

PARTICIPANTS

Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older.

METHODS

Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen.

MAIN OUTCOME MEASURES

Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112.

RESULTS

Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112.

CONCLUSIONS

Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

摘要

目的

评估抑制血管生成素-2 和 VEGF-A 的双特异性抗体 faricimab 的 2 年疗效、持久性和安全性。

设计

TENAYA（ClinicalTrials.gov 标识符，NCT03823287）和 LUCERNE（ClinicalTrials.gov 标识符，NCT03823300）是设计相同的、随机的、双盲的、活性对照的 3 期非劣效性试验。

参与者

未经治疗的年龄相关性黄斑变性（nAMD）患者，年龄 50 岁及以上。

方法

患者随机（1:1）接受玻璃体腔内 faricimab 6.0 mg，每 16 周（Q16W）或 aflibercept 2.0 mg 每 8 周（Q8W）。根据第 20 周和第 24 周的方案定义的疾病活动情况，对 faricimab 进行固定剂量治疗，直至第 60 周，随后在第 108 周根据个性化治疗间隔方案进行治疗和延长。

主要观察指标

疗效分析包括在第 2 年（在第 104、108 和 112 周的平均值）时最佳矫正视力（BCVA）从基线的变化以及在第 112 周时接受 Q16W、每 12 周（Q12W）和 Q8W 剂量的意向治疗人群中的比例。安全性分析包括在第 112 周研究眼的眼部不良事件（AE）。

结果

在 TENAYA/LUCERNE 治疗的 1326 例患者中，1113 例（83.9%）完成了治疗（n=555 例 faricimab；n=558 例 aflibercept）。在 TENAYA 中，与 aflibercept 组相比，faricimab 组的 BCVA 从基线到 2 年的变化具有可比性（调整后的平均变化分别为+3.7 个字母[95%置信区间（CI），+2.1 至+5.4]和+3.3 个字母[95%CI，+1.7 至+4.9]；平均差异，+0.4 个字母[95%CI，-1.9 至+2.8]）和 LUCERNE（调整后的平均变化分别为+5.0 个字母[95%CI，+3.4 至+6.6]和+5.2 个字母[95%CI，+3.6 至+6.8]；平均差异，-0.2 个字母[95%CI，-2.4 至+2.1]）。在 TENAYA 和 LUCERNE 的第 112 周，分别有 59.0%和 66.9%的患者达到了 Q16W faricimab 剂量，从第 1 年开始增加，分别有 74.1%和 81.2%的患者达到了 Q12W 或更长的剂量。在第 112 周时，TENAYA（分别为 55.0%和 56.5%的患者）和 LUCERNE（分别为 52.9%和 47.5%的患者）的研究眼的眼部 AE 在 faricimab 和 aflibercept 组之间具有可比性。