In its decanting of the BRUNELLO trial of remigromig for diabetic macular oedema (DME), MSD seems to have left observers contemplating a glass half empty.

在公布remigromig治疗糖尿病性黄斑水肿（DME）的BRUNELLO试验结果时，默沙东似乎让观察者们感到失望。

Expectations for Wnt pathway-targeting trispecific antibody remigromig (MK-3000, formerly known as EYE103) were riding high last month after MSD reported

上月，在默沙东报告之后，市场对靶向Wnt通路的三特异性抗体remigromig（MK-3000，前称EYE103）的期望高涨

topline results

总体结果

from the phase 2b/3 trial, saying that, after a year, it had performed at least as well as the active control at maintaining vision in

来自2b/3期试验，称一年后，其在维持视力方面至少不劣于活性对照药

DME

测距仪

patients.

患者。

Over the weekend, however, MSD presented fuller results from BRUNELLO at the American Academy of Ophthalmology (AAO) annual congress, which dampened that initial enthusiasm.

然而，在周末举行的美国眼科学会（AAO）年会上，默沙东公布了BRUNELLO研究的更完整结果，这给最初的热情泼了冷水。

Chief among the concerns was the rate of proliferative diabetic retinopathy (PDR) – a severe stage of diabetic eye disease where abnormal new blood vessels grow on the surface of the retina – which was seen in 6.7% of patients taking a 0.5 mg dose of remigromig and 6.1% with a 0.8 mg dose, and just 0.9% of the active control group, who were treated with VEGF inhibitor ranibizumab..

主要关注的问题是增生性糖尿病视网膜病变（PDR）的发生率，这是一种严重的糖尿病眼病阶段，表现为视网膜表面异常新生血管生长。在服用0.5毫克剂量remigromig的患者中，该病变发生率为6.7%，在服用0.8毫克剂量的患者中为6.1%，而在接受VEGF抑制剂雷珠单抗治疗的活性对照组中仅为0.9%。

The company thinks that the disparity could be related to remigromig's mechanism, as, unlike VEGF inhibition, it does not block the formation of new blood vessels. The higher rates could therefore be a manifestation of the natural progression of the disease rather than a side effect, according to MSD, which is exploring that hypothesis in further studies..

该公司认为，这种差异可能与remigromig的作用机制有关，因为与VEGF抑制不同，它并不阻断新血管的形成。因此，据默沙东（MSD）称，较高的发生率可能是疾病自然进展的表现，而非副作用；该公司正在通过进一步研究验证这一假设。

At the same time, however, the efficacy data did not point to a significant hike in efficacy that could offset the PDR finding. On the primary endpoint of best corrected visual acuity (BCVA) at one year, there was a 9.1-point gain for remigromig 0.5 mg, 8.7 points with remigromig 0.8 mg, and 11.8 points with ranibizumab, which met the non-inferiority criteria but does not give a compelling reason to opt for remigromig over the older – and likely cheaper – off-patent alternative..

然而，与此同时，疗效数据并未显示疗效有显著提高，从而抵消PDR研究结果的影响。在一年期最佳矫正视力（BCVA）这一主要终点指标上，remigromig 0.5 mg组提高了9.1分，remigromig 0.8 mg组提高了8.7分，而ranibizumab组提高了11.8分；虽然达到了非劣效性标准，但并未提供充分理由选择remigromig而非更老旧且可能更便宜的仿制药替代方案。

Lead BRUNELLO investigator Donald D'Amico of Weill Cornell Medicine made the case for the drug at AAO, pointing out that up to two-thirds of DME patients fail to achieve clinically meaningful vision gains after one year of VEGF inhibitor therapy.

BRUNELLO研究的主要研究者、来自威尔康奈尔医学院的唐纳德·达米科在美国眼科学会（AAO）会议上阐述了该药物的应用理由，他指出，高达三分之二的糖尿病性黄斑水肿（DME）患者在接受一年的血管内皮生长因子（VEGF）抑制剂治疗后，未能获得具有临床意义的视力改善。

'These findings ‒ which demonstrate for the first time that a biologic targeting the Wnt pathway can achieve visual acuity comparable to an established anti-VEGF therapy ‒ support continued evaluation of this novel approach,' he said.

“这些发现首次证明，靶向Wnt信号通路的生物制剂能够达到与已确立的抗VEGF疗法相当的视力效果，支持对这一新颖方法进行持续评估。”他说。

MSD is running a second phase 2b/3 trial of the Wnt drug in DME, called BAROLO, which is due to read out next year, as well as a mid-stage study (SUPER TUSCAN) in neovascular AMD and retinal vein occlusion (RVO).

默沙东正在开展其Wnt通路药物针对糖尿病性黄斑水肿（DME）的第二项2b/3期临床试验（名为BAROLO），该试验预计将于明年公布结果；同时，该公司还在进行一项针对新生血管性年龄相关性黄斑变性（nAMD）和视网膜静脉阻塞（RVO）的中期研究（名为SUPER TUSCAN）。

The data prompted analysts at BMO Capital Markets to say they now view remigromig as having 'limited competitive potential' in DME. MSD – known as Merck & Co in the US and Canada – added remigromig to its pipeline as part of its acquisition of EyeBio in a $3 billion deal in 2024.

这些数据促使蒙特利尔银行资本市场的分析师表示，他们现在认为remigromig在DME领域的“竞争潜力有限”。MSD（在美国和加拿大称为默克公司）在2024年以30亿美元收购EyeBio的交易中，将remigromig纳入其研发管线。

Analysts have previously said they viewed remigromig as a key component of MSD's strategic goal to achieve $70 billion in annual sales by the 2030s to offset the upcoming patent expiration of $32 billion cancer immunotherapy blockbuster Keytruda (pembrolizumab).

分析师此前表示，他们认为remigromig是默沙东（MSD）战略目标的关键组成部分，旨在到2030年代实现700亿美元的年销售额，以抵消其320亿美元的癌症免疫疗法重磅药物Keytruda（帕博利珠单抗）即将面临的专利到期影响。

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