Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Viatris Inc, Canonsburg, Pennsylvania.
JAMA Ophthalmol. 2024 Oct 1;142(10):952-960. doi: 10.1001/jamaophthalmol.2024.3458.
Biosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME).
To compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME.
DESIGN, SETTING, AND PARTICIPANTS: This was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021.
Formulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52.
The primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of -3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs).
A total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, -1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was -112 (7) μm vs -124 (7) μm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 μm; 90% CI, -3 to 26 μm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms.
MYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept.
ClinicalTrials.gov Identifier: NCT03610646.
生物类似药可能是生物原创产品的低成本替代品，具有扩大可及性或降低经济负担的潜力，但在糖尿病性黄斑水肿（DME）中尚未对 aflibercept 进行评估。
比较 MYL-1701P（一种 aflibercept 生物类似药）与参考 aflibercept（Eylea[Regeneron]）在 DME 中的疗效和安全性。
设计、地点和参与者：这是一项在美国、欧洲、日本和印度的 77 个中心进行的双盲、随机临床试验。分析对象包括年龄在 18 岁及以上的 1 型或 2 型糖尿病患者，研究眼的最佳矫正视力（BCVA）字母评分使用早期糖尿病视网膜病变研究（ETDRS）图表为 73 至 38。研究数据于 2021 年 10 月至 12 月进行分析。
每 4 周连续玻璃体腔内注射 MYL-1701P（0.5 毫升小瓶）或参考 aflibercept 5 次，每次 0.5 毫克，然后每 8 周注射一次，直至第 52 周。
主要结局是从基线开始 8 周时最小平方均值（SE）变化的调整差异，等效范围为-3 至+3 个字母。次要结局包括中央视网膜神经纤维层厚度（CST）、BCVA、52 周内注射次数、不良事件（AE）发生率和抗药物抗体（ADA）的变化。
共纳入 355 名参与者（平均[SD]年龄，62.2[9.2]岁；男性 216 名[60.8%]），随机分为 MYL-1701P（179 名[50.4%]）和 aflibercept（176 名[49.6%]）组。第 8 周时，BCVA 的平均（SE）变化分别为 MYL-1701P 组 6.60（0.55）个字母和 aflibercept 组 6.56（0.55）个字母。调整后的平均差异为 0.04 个字母（90%置信区间，-1.16 至 1.24 个字母）符合主要结局。第 8 周时，CST 的平均（SE）变化分别为 MYL-1701P 组-112（7）μm和 aflibercept 组-124（7）μm（调整后的平均差异，12μm；90%置信区间，-3 至 26μm）。MYL-1701P 和 aflibercept 组治疗后出现的眼部不良事件发生率分别为 30.9%（178 名中的 55 名）和 29.5%（176 名中的 52 名），严重眼部不良事件发生率分别为 0.6%（178 名中的 1 名）和 1.1%（176 名中的 2 名），非眼部不良事件发生率分别为 65.2%（178 名中的 116 名）和 65.3%（176 名中的 115 名），严重非眼部不良事件发生率分别为 16.9%（178 名中的 30 名）和 11.9%（176 名中的 21 名）。MYL-1701P 和 aflibercept 组的平均（SD）总注射次数分别为 8.4（2.1）和 8.7（1.8）。治疗诱导或治疗增强型 ADA 的发生率分别为 2.8%（177 名中的 5 名）和 5.7%（176 名中的 10 名）。
Myl-1701P 在疗效方面表现出临床等效性，安全性和免疫原性与参考 aflibercept 相当。这些发现支持使用 MLY-1701P 作为参考 aflibercept 的替代品。
ClinicalTrials.gov 标识符：NCT03610646。
