Wnt drug gives MSD first eye disease win after EyeBio deal
MSD's return to the ophthalmology field after decades of absence, via the acquisition of EyeBio in a $3 billion deal in 2024, has been charged up with a positive phase 3 trial in diabetic macular oedema (DME).
The phase 2b/3 BRUNELLO study of remigromig (MK-3000, formerly known as EYE103) showed that two doses of the Wnt pathway-targeting trispecific antibody were both at least as effective as the active control, the VEGF inhibitor ranibizumab, in maintaining vision at 52 weeks in adult DME patients.
Remigromig introduces the first entirely new mechanism of action for retinal vascular diseases in over two decades, and is thought to work by maintaining the blood-retinal-barrier and preventing the leakage of retinal fluid that is seen in DME, as well as other diseases like neovascular age-related macular degeneration (AMD).
That leakage often persists despite treatment with VEGF inhibitors like ranibizumab, and the hope is that remigromig could find a role as an alternative or addition to these drugs, assuming it continues to show efficacy and safety in future trial readouts.
"Despite available therapies, up to 40% of patients with [DME] do not fully respond and remain at risk of continued vision loss," said Dr David Guyer, chief executive officer of EyeBio, which operates as a wholly-owned subsidiary of MSD.
Safety signal?
One potential fly in the ointment for MSD was that remigromig was associated with higher rates of proliferative diabetic retinopathy (PDR) – a severe stage of diabetic eye disease where abnormal new blood vessels grow on the surface of the retina – as well as vitreous haemorrhage and treatment discontinuations due to adverse events compared to ranibizumab.
Those could be related to the drug's mechanism, as - unlike VEGF inhibition - it does not block the formation of new blood vessels, so the higher rates could be a manifestation of the natural progression of the disease, rather than a side effect of the drug. Nevertheless, safety looks likely to be scrutinised when the full results from BRUNELLO are released in full at the American Academy of Ophthalmology (AAO) congress next month, and in future trial readouts.
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).
At stake is a slice of the massive market for retinal vascular disease treatments, currently led by Bayer and Regeneron's Eylea (aflibercept) VEGF inhibitor range, which made almost $8 billion in global sales last year. Following after is Roche's VEGFxAng-2 bispecific antibody Vabysmo (faricimab), which brought in around $5.2 billion.
Analysts said remigromig is 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).
Photo by Andrei Castanha on Unsplash
