Retina Society 2026: LUGANO secondary data show reduced treatment burden with vorolanib insert despite missed primary end point

At the Retina Society 59th Annual Scientific Meeting in Los Angeles, California, Charles Wykoff, MD, PhD, presented secondary end point and safety data from the phase 3 LUGANO trial. The trial compared vorolanib intravitreal insert (Duravyu; EyePoint) with aflibercept 2 mg (Eylea; Regeneron) dosed every 8 weeks in patients with wet age-related macular degeneration (AMD). In an interview with Modern Retina, Wykoff discussed the trial design, the treatment burden findings, and the adverse event profile.

Trial design

Patients were randomized equally to vorolanib intravitreal insert or aflibercept. Of those enrolled, 75% were treatment naive and 25% had been previously treated. All patients received 3 monthly aflibercept loading doses. The aflibercept arm then continued fixed dosing every 8 weeks. The vorolanib arm received the insert with the third loading dose at week 8 and was redosed at week 32.

Patients in both arms could receive supplemental aflibercept under either of 2 criteria:

• A loss of more than 5 letters with a 75-μm increase in central subfield thickness (CST)
• Development of vision-threatening hemorrhage

Treatment burden

Annualized injection burden excluded loading doses. It was 5.3 injections in the aflibercept arm and 3.1 in the vorolanib arm, a 42% reduction. Patients in the vorolanib arm received a mean of 1.1 annualized supplemental injections.

Among vorolanib-treated patients:

• 76% were supplement free through week 32.
• 54% were supplement free through week 56.
• 79% received 0 or 1 supplement through week 56.

About 10% of the aflibercept arm also received supplemental therapy.

In the supplement-free subgroup, visual acuity trajectories overlapped through week 32. At week 56, mean gains were 6.4 letters with aflibercept and 4.7 letters with vorolanib. With the insert, CST held near the upper bound of the sawtooth pattern seen with aflibercept dosing.

Primary end point

LUGANO did not meet its primary end point of mean change in best-corrected visual acuity. Wykoff noted a possible imbalance: more patients in the vorolanib arm lost vision from causes other than wet AMD. He said the paired LUCIA trial, expected to read out in the fourth quarter of 2026, will be key to confirming that observation. "It really kind of needs to be successful in the second trial without any caveats," he said.

Safety

Vitreous floaters occurred in 9% of the vorolanib arm vs 3.6% of the aflibercept arm. Wykoff attributed the difference to the visible biodegradable insert. No insert migration into the anterior chamber, anterior chamber opacities, or free-floating particles occurred. Wet AMD adverse events (7.1% vs 1.4%) reflected undercontrolled eyes that needed supplemental injections, he said.

The other notable events were:

• Endophthalmitis: 2 cases, 1 culture negative and 1 culture positive for Staphylococcus epidermidis. Both resolved, with visual acuity returning to within 3 letters of baseline.
• Retinal detachment: 2 cases, each repaired with 1 vitrectomy. One phakic vorolanib-treated patient lost 40 letters at week 56, which Wykoff attributed to cataract and epiretinal membrane.
• Intraocular inflammation: 2 moderate cases, 1 in each arm. Both were treated with topical steroids.

Clinical takeaway

"Treatment burden is a real issue for our patients," Wykoff said. He added that the data point to a subpopulation that maintains good control with dosing every 6 months. The open question is how to identify those patients prospectively. Tyrosine kinase inhibitor trials are also ongoing in diabetic retinopathy and diabetic macular edema.