Lucie Guo, MD
Byers Eye Institute, Stanford, CA
The Saturday late breaking session at the 2024 Retina Society meeting featured an interesting discussion on new, exciting biologics.
The session began with Dennis Marcus, MD who presented the safety and efficacy of the intravitreal OTX-TKI implant, one-year results from the HELIOS Phase I trial. OTX-TKI (axitinib) is a sustained-release tyrosine kinase inhibitor that enables internal blockade of multiple VEGF pathways. A multi-center, double-masked, 2:1 randomized Phase I trial was performed in patients with moderately severe to severe NPDR (DRSS levels of 47 or 53) with CI-DME (as assessed by investigator) and baseline visual acuity of approximately 20/40 or better. The data included 21 patients, who received either OTX-TKI (n=13) or sham procedure (n=8). The primary outcome was safety and tolerability, and secondary outcomes included changes in the Diabetic Retinopathy Severity Scale (DRSS), best corrected visual acuity (BCVA), central subfield thickness (CST), and rates of needing rescue therapy.
At 48 weeks, there were no reported intraocular inflammation events (iritis, vitritis, or retinal vasculitis) in the OTX-TXI group. At 48 weeks, 23% of the OTX-TKI arm had a ≥2 step DRSS improvement (and 46.2% had a 1 or ≥2 step DRSS improvement), versus 0% in the sham group. No one in the OTX-TKI group showed worsening of retinopathy by DRSS, whereas 12.5% of the sham arm did have worsening. OTX-TKI treated patients demonstrated stable vision through 48 weeks, and there was a strong trend toward CST reduction in the macular volume in the OTX-TKI group. No OTX-TKI patients developed PDR or CI-DME through week 48, whereas 37.5% in the sham control arm did. No patients required rescue therapy in either arm. Overall, this study showed that a single OTX-TKI injection showed durable fluid suppression and more stable fluid control through week 48. It is interesting to note that whereas prior tests of OTX-TKI in age-related macular degeneration patients required loading doses of aflibercept, it seems that such concurrent usage of traditional anti-VEGF therapeutics does not appear necessary in the NDPR/CI-DME population.
Next, Dr. Durga Borkar presented data on Fas inhibition with intravitreal ONL1204 for the treatment of macula-off rhegmatogenous retinal detachments (RRDs). ONL1204 is a first-in-class neuroprotective agent that inhibits the Fas receptor, thus blocking the activation of the Fas pathway and the apoptosis pathway responsible for death of retinal cells. There is motivation to test neuroprotective agents in macula-off RRDs since patients often have significant visual loss despite the surgical repair of the detachment. This was a sham-controlled, single masked, dose-ranging, multicenter study in which patients either received a 20ug, 200ug or sham at the time of diagnosis of macula-off RRD prior to surgical repair. The primary endpoint was contrast sensitivity (area under the log contrast sensitivity function curve, “AULCSF”) as measured with the AST Manifold Contrast Vision Meter, at week 24.
There were 136 patients enrolled: 45 received 200µg, 46 received 50µg, and 45 received sham. At 24 weeks post-surgery, contrast sensitivity was similar between the groups, so the study did not meet its primary endpoint. However, further analyses showed that ONL1204 treated eyes benefited from 1-2 lines of improved vision. Of note, 52.6% of patients in the ONL1204 200µg group (and 50% of patients in the 50µg group) had duration of macula-off status of >8 days, compared to 25.6% of patients in the sham group. Re-detachment rates were not statistically significant across the groups, and the drug appeared well-tolerated without major safety issues reported.