MSD data reveal undercuts eye drug remigromig's potential

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.

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

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

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.

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.

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.

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.

"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.

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).

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.

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).

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