目的:评估2年疗效,耐用性,和双特异性抗体的安全性,Faricimab,抑制血管生成素-2和血管内皮生长因子-A。
方法:TENAYA(NCT03823287)和LUCERNE(NCT03823300)设计相同,随机化,双面蒙面,在全球271个地点进行主动比较控制的3期非劣效性试验。
方法:初治年龄≥50岁的新生血管性年龄相关性黄斑变性(nAMD)患者。
方法:随机(1:1)接受玻璃体内法罗单抗6.0mg至每16周(Q16W)或阿柏西普2.0mg每8周(Q8W)。Faricimab基于方案定义的疾病活动在第20周和第24周至第60周的固定剂量,通过基于治疗和扩展的个性化治疗间隔方案随访至第108周。
方法:功效分析包括2年最佳矫正视力(BCVA)相对于基线的变化(平均第104、108和112周)以及Q16W患者的比例,每12周(Q12W),意向治疗人群在第112周给予Q8W。安全性分析包括在第112周研究结束时接受≥1剂量研究治疗的患者的研究眼睛中的眼部不良事件(AE)。
结果:在所有试验中接受治疗的1326名患者中,1113(83.9%)完成了研究治疗(n=555法里单抗和n=558阿柏西普)。在TENAYA中,faricimab和aflibercept在2年时从基线的BCVA变化相当(调整后的平均变化[95%置信区间(CI)]+3.7字母[2.1至5.4]和3.3字母[1.7至4.9],分别;平均差[95%CI]0.4个字母[-1.9至+2.8])和LUCERNE(调整后的平均变化[95%CI]+5.0个字母[+3.4至+6.6]和+5.2[+3.6至+6.8],分别;平均差[95%CI]-0.2个字母[-2.4至+2.1])。分别在TENAYA和LUCERNE的第112周,59.0%和66.9%实现了Q16W法利单抗给药,从第1年开始增加,74.1%和81.2%达到≥Q12W剂量。直到第112周,TENAYA(55.0%和56.5%的患者)和LUCERNE(52.9%和47.5%的患者)中的faricimab和aflibercept在研究眼中的眼部AE相当。
结论:基于nAMD疾病活动的基于治疗和扩展的法利单抗治疗在第2年保持视力增长,大多数患者达到延长给药间隔。
OBJECTIVE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A.
METHODS: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials.
METHODS: 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.
METHODS: 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.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.