Merck & Co. (NYSE: MRK) dropped topline results Thursday from its pivotal Phase 2b/3 BRUNELLO trial, and the headline is a familiar one in biotech: the investigational drug works about as well as the incumbent. The details underneath are where things get interesting.

The trial tested remigromig in adults with diabetic macular edema, or DME. For the uninitiated, DME is one of those diabetes complications that doesn't get as much airtime as, say, neuropathy, but it's serious. High blood sugar damages the tiny blood vessels in the retina, they leak fluid into the macula, the macula swells, and sharp central vision goes sideways.

BRUNELLO is the first of two Phase 2b/3 trials evaluating remigromig (MK-3000, formerly EYE103), an investigational tetravalent, tri-specific antibody designed to activate the Wingless-related integration site (Wnt) pathway. That pathway is involved in repairing and maintaining the blood-retinal barrier, which is exactly the kind of thing you want working properly if you'd like your retina to stay dry.

52 Weeks, Two Doses, One Active Control

At 52 weeks, both doses of remigromig (0.5 mg and 0.8 mg) independently demonstrated non-inferiority to active control 0.5 mg Roche Holding AG's (OTC: RHHBY) unit Genentech's Lucentis (ranibizumab) for mean change from baseline in best-corrected visual acuity (BCVA) in patients with DME.

Non-inferiority, for those keeping score at home, means remigromig didn't lose to Lucentis. It didn't necessarily beat it either, but in a market where Lucentis is a well-established standard, matching it is a legitimate result.

The asterisk comes on the safety side. Higher rates of proliferative diabetic retinopathy (PDR), vitreous hemorrhage, and treatment discontinuations due to adverse events were observed in the remigromig treatment arms compared with ranibizumab.

Both doses were generally well tolerated, and Merck says further analyses are underway to characterize these findings. Translation: the efficacy story is clean, the safety story needs a closer look.

Building Out the Ophthalmology Pipeline

The BRUNELLO topline results build on Merck's advancing ophthalmology pipeline, which is aimed at promoting retinal recovery by addressing specific retinal diseases associated with vascular leakage and neovascularization, including DME, neovascular (wet) age-related macular degeneration (NVAMD) and macular edema secondary to retinal vein occlusion (RVO).

Beyond BRUNELLO, remigromig is being evaluated in the ongoing pivotal Phase 2b/3 BAROLO study in patients with DME and in a Phase 2 proof-of-concept study (SUPER TUSCAN) in patients with NVAMD and RVO.

Merck is also developing MK-8748 (also known as Tiespectus, EYE201), an investigational bispecific antibody with a dual mechanism that directly activates the Tie2 pathway and inhibits VEGF, with the goal of stabilizing retinal and choroidal blood vessels and reducing fluid accumulation in the macula.

MK-8748 is currently being studied in two pivotal Phase 2b/3 trials for the treatment of NVAMD, TORRONTES and MALBEC, and in two pivotal Phase 3 studies for the treatment of DME, SANGIOVESE and SYRAH. That is a lot of trial names, and a lot of shots on goal.

MRK Price Action: Merck & Co shares were up 0.28% at $148.49 at the time of publication on Thursday, according to market data.