Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
West Texas Retina Consultants, Abilene, Texas.
Ophthalmology. 2019 Aug;126(8):1155-1170. doi: 10.1016/j.ophtha.2019.03.023. Epub 2019 Mar 21.
The phase 2 BOULEVARD trial compared safety and efficacy of faricimab, a novel bispecific antibody targeting angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A), with ranibizumab in patients with diabetic macular edema (DME).
The BOULEVARD trial (ClinicalTrials.gov identifier, NCT02699450) was a prospective, randomized, active comparator-controlled, double-masked, multicenter, phase 2 study conducted at 59 sites in the United States.
The trial enrolled patients 18 years of age or older with center-involving DME, best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and central subfield thickness (CST) of 325 μm or more.
Anti-VEGF treatment-naïve patients were randomized 1:1:1 to intravitreal 6.0 mg faricimab, 1.5 mg faricimab, or 0.3 mg ranibizumab, and patients previously treated with anti-VEGF were randomized 1:1 to 6.0 mg faricimab or 0.3 mg ranibizumab. Patients were dosed monthly for 20 weeks, followed by an observation period up to week 36 to assess durability.
The prespecified primary outcome measure was mean change in BCVA from baseline at week 24 for faricimab versus ranibizumab in treatment-naïve patients. Key secondary and exploratory outcome measures included CST, Diabetic Retinopathy Severity Scale (DRSS) score, and durability as assessed by time to re-treatment.
The trial enrolled 229 patients (168 treatment-naïve and 61 previously treated with anti-VEGF). In treatment-naïve patients, 6.0 mg faricimab, 1.5 mg faricimab, and 0.3 mg ranibizumab resulted in mean improvements of 13.9, 11.7, and 10.3 ETDRS letters from baseline, respectively. The 6.0-mg faricimab dose demonstrated a statistically significant gain of 3.6 letters over ranibizumab (P = 0.03). In both patient populations, faricimab resulted in dose-dependent reductions in CST, improvements in DRSS score, and longer time to re-treatment during the observation period compared with ranibizumab. Faricimab showed no new or unexpected safety signals.
The BOULEVARD trial met its primary end point; faricimab demonstrated statistically superior visual acuity gains versus ranibizumab at week 24 in treatment-naïve patients. Central subfield thickness reduction, DRSS score improvement, and extended durability outcomes support the primary outcome. These findings suggest the benefit of simultaneous inhibition of angiopoietin-2 and VEGF-A with faricimab for patients with DME.
2 期 BOULEVARD 试验比较了新型双特异性抗体 faricimab（靶向血管生成素-2 和血管内皮生长因子-A（VEGF-A））与 ranibizumab 在糖尿病性黄斑水肿（DME）患者中的安全性和疗效。
BOULEVARD 试验（ClinicalTrials.gov 标识符，NCT02699450）是一项前瞻性、随机、活性对照、双盲、多中心、2 期研究，在美国 59 个地点进行。
该试验纳入了年龄在 18 岁或以上、有中心性 DME、最佳矫正视力（BCVA）为 73 至 24 个早期治疗糖尿病性视网膜病变研究（ETDRS）字母，以及中央视网膜厚度（CST）大于 325μm的患者。
抗 VEGF 治疗初治患者按 1:1:1 随机分为玻璃体腔内 6.0mg faricimab、1.5mg faricimab 或 0.3mg ranibizumab，先前接受过抗 VEGF 治疗的患者按 1:1 随机分为 6.0mg faricimab 或 0.3mg ranibizumab。患者每月给药一次，共 20 周，随后进行长达 36 周的观察期，以评估持久性。
主要预先设定的终点是初治患者在第 24 周时与 ranibizumab 相比，BCVA 的平均变化。关键次要和探索性终点包括 CST、糖尿病视网膜病变严重程度评分（DRSS）和作为再治疗时间的持久性。
该试验纳入了 229 名患者（168 名初治和 61 名先前接受过抗 VEGF 治疗）。在初治患者中，6.0mg faricimab、1.5mg faricimab 和 0.3mg ranibizumab 分别使基线时的 BCVA 平均提高了 13.9、11.7 和 10.3 ETDRS 字母。6.0mg faricimab 剂量与 ranibizumab 相比，在视力上有统计学意义的 3.6 个字母的获益（P=0.03）。在这两个患者群体中，与 ranibizumab 相比，faricimab 导致 CST 剂量依赖性降低、DRSS 评分改善和观察期间再治疗时间延长。faricimab 没有显示出新的或意外的安全性信号。
BOULEVARD 试验达到了其主要终点；在初治患者中，faricimab 在第 24 周时与 ranibizumab 相比，视力提高具有统计学意义。CST 减少、DRSS 评分改善和延长的持久性结果支持主要终点。这些发现表明，faricimab 同时抑制血管生成素-2 和 VEGF-A 对 DME 患者有益。
