David Xu, MD
Wills Eye Hospital/Mid Atlantic Retina
The second Late Breaking Developments section was an exciting and action-packed presentation from several leaders in the field that discussed potentially upcoming therapies in the pipeline for patients with wet macular degeneration and geographic atrophy.
Intravitreal Sunitinib Malate Depot (GB-102)
Dr. Veveral Sheth was the first to present on intravitreal sustained-release sunitinib (GB-102), a tyrosine kinase inhibitor inhibiting upstream all forms of VEGF, for treatment of wet AMD in a phase 2B trial of 50 patients. The drug is injected intravitreally in the office and has a sustained release depot formulation. Wet AMD patients with at least 3 prior anti-VEGF injections were enrolled in the 18 month comparative study. Treatment was performed on day 1 with the opportunity for another treatment at month 6. The primary endpoint was time to first recue injection and secondary endpoints were change in baseline BCVA and CST. Overall, GB-102 reduced injection frequency by 63%. In the 1mg GB-102 arm, 42% of patients required rescue therapy before month 6 while 50% of patients did not need rescue through month 18. Adverse events included intraocular inflammation and product residue found in the anterior chamber. Based on the encouraging efficacy results and adverse event data, new formulations of the medications are being developed.
EYP-1901, an intravitreal tyrosine kinase inhibitor for wet AMD
Dr. David Boyer reported on the phase 1 DAVIO trial of intravitreal EYP-1901 (vorolanib), a tyrosine kinase inhibitor, delivered via an erodible sustained-release pellet for patients with wet AMD. A oral formulation of the drug had previously been studied for tumor although it was discontinued due to systemic adverse events. In this phase 1 trial, four escalating doses were evaluated in 17 patients with non-naïve wet AMD. The primary endpoint was safety and secondary endpoints were change in BCVA and CST. The average BCVA and CST were stable and maintained over 6 months. The rescue free rate was 53% months at 6 months and the median time to rescue was 6 months. Importantly, &o serious ocular safety events were reported.
ONS-5010, phase 3 results of an ophthalmic bevacizumab
The next presentation was delivered by Dr. Firas Rahhal who presented on ONS-5010 (bevacizumab-vikg), an ophthalmic bevacizumab, in the phase 3 NORSE 2 trial for wet AMD. The efficacy of off-label compounded bevacizumab has been evaluated in previous clinical trials such as the CATT study. This 12-month study compared two distinct dosing strategies between the treatment arms, consisting of monthly bevacizumab-vikg versus quarterly ranibizumab dosing after 3 monthly loading injections similar to the PIER protocol. The primary outcome was the proportion of patients who gained >= 15 letters, the mean change in BCVA from baseline to month 11 (where BCVA analysis was performed was performed) and the frequency of adverse events. 228 patients were enrolled in a 1:1 randomization between ONS-5010 and ranibizumab arms. The study met its primary endpoint and found a significantly greater proportion of 3 lines gained in the ONS-5010 treatment protocol (42% of subjects) compared to the ranibizumab protocol (23%). One case of iritis was reported in the ONS-5010 arm.
Nascent GA and intermediate AMD progression in the GATHER1 trial
Finally, we wrap up the session with a great talk by Dr. David Lally. This was a post hoc evaluation of the GATHER1 data, a phase 2/3 study of intravitreal avacincaptad pegol for geographic atrophy. Dr. Lally performed a retrospective evaluation using OCT-based consensus definitions of geographic atrophy and impending GA, complete and incomplete RPE and outer retinal atrophy (cRORA and iRORA) . Based on this, two analyses were performed with respect to the avacincaptad trial. First, it evaluated whether treatment can reduce progression from iRORA to cRORA. Second, it evaluated whether treatment can reduce the progression of drusen to iRORA. The first analysis demonstrated a 50% reduction in progression from iRORA to cRORA and the trajectory of cRORA development between the treatment and sham groups appeared to clearly separate. However, Dr. Lally notes that no statistics were performed as this was an exploratory analysis. A similar trend was noted from progression of drusen to iRORA. The authors are hopeful that this generates new lines of inquiry to study atrophic AMD in its earlier stages.