Positive outcomes seen with combined OPT-302, aflibercept for DME in phase 2a trial
The combination of aflibercept and OPT-302, a blocker of VEGF-C and VEGF-D, showed potential for improved visual and anatomic outcomes in patients with diabetic macular edema.
The outcomes of phase 1b and 2a trials, presented at the virtual American Academy of Ophthalmology annual meeting, look promising and may fulfill an unmet need for those patients who do not respond well to anti-VEGF therapy, David S. Boyer, MD, said.
“Almost 40% of DME patients do extremely well with anti-VEGFs, but about 35% gain less than four letters. Combination therapy might improve these results,” he said.
In the phase 1b dose-escalation study, 0.3 mg, 1 mg or 2 mg of OPT-302 (Opthea) was used in combination with 2 mg of Eylea (aflibercept, Regeneron). The drug was well tolerated up to 2 mg with no adverse events, and a significant improvement of 14 letters was achieved with the 2 mg dose. Based upon this, the 2 mg dose of OPT-302 was used in combination with aflibercept in the phase 2a study and compared with aflibercept alone. Three injections were given at 4-week intervals with a readout at 12 weeks.
“There were no safety concerns, and 53% of the patients in the combination group achieved a greater than five letter improvement. However, if you look at the change at week 12 from baseline, the two groups were very similar, with a slight trend for greater than 10 or 15 letters of gain and less vision loss in the combination group. The combination therapy also showed a better anatomic response in the central subfield thickness,” Boyer said.
He said that this was a heterogeneous group of patients, previously treated with diverse agents, dosing schedules and number of injections. A post hoc analysis was therefore performed on the subgroup of 35 patients who received only aflibercept before enrolling in the trial.
“The mean change in BCVA at week 12 in this more homogeneous group showed an improvement from 3.4 to 6.6 letters. The percentage of patients gaining 10 or 15 letters from baseline or losing vision all favored the combination group, with almost 27% of patients gaining 10 letters,” Boyer said.
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Boyer DS. Phase 1b/2a DME study results of OPT-302 to block VEGF-C/-D in combination with aflibercept. Presented at: American Academy of Ophthalmology annual meeting; Nov. 13-15, 2020 (virtual meeting).
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