Improvements in visual acuity (VA), and retinal swelling (central subfield thickness (CST) and sub-retinal fluid (SRF)) have been observed in a Phase 1/2A clinical trial of OPT-302, a novel VEGF-C/D ‘Trap’ therapy for wet age-related macular degeneration (wet AMD). Opthea Limited, the developer of OPT-302, has stated the findings suggest additional clinical benefit can be achieved with more complete suppression of
VEGF-A and VEGF-C/D.
The study has been conducted at 14 sites in the US and run under an Investigational New Drug (IND) program with the Food and Drug Administration (FDA). OPT-302 demonstrated clinical activity in all patient groups investigated, including naïve and prior-treated patients in both the monotherapy and combination OPT-302 + Lucentis groups.
Dr. Megan Baldwin, CEO of Opthea said, “the data warrants Opthea expanding its clinical development program to progress OPT-302 as a novel combination therapy for the treatment of wet AMD as well as other eye diseases, including diabetic macular oedema”.
The Phase 1/2A study met its primary safety objective, with intravitreal injections of OPT-302 being well tolerated both as monotherapy and in combination with standard of care Lucentis. No treatment related serious adverse events, systemic adverse events or dose limiting toxicities were observed.
the data warrants Opthea expanding its clinical development program to progress OPT-302 as a novel combination therapy
Overall, 90 per cent of patients (44/49) evaluable at week 12 maintained or improved VA at week 12, compared to baseline. Of the 49 patients, 100 per cent had stabilisation or improvement in visual acuity (defined as less than or equal to 15 letter loss on the ETDRS eye chart).
In treatment naïve patients who received combination OPT-302 + Lucentis, the mean change in VA from baseline at week 12 was +10.8 letters (n=18).
The visual acuity improvements were seen as early as four weeks and continued to increase throughout the study to week 12. Additionally, 33 per cent of these treatment naïve patients showed BCVA gains of ≥ 15 letters (≥ 3 lines) on a standard eye-chart at week 12.
The mean change in VA from baseline at week 12 in previously treated patients with difficult to treat wet AMD was +4.9 letters (n=19 evaluable), despite long term prior treatment with anti-VEGF-A therapy (mean number of prior treatment injections = 17, range 3, 76).
The mean central subfield thickness (CST) decreased in all combination OPT-302 + Lucentis treatment groups at week 12. The mean CST reduced to 283 μM at week 12 in treatment-naïve patients. In patients who showed a sub-optimal response to prior anti-VEGF-A therapy, mean CST decreased by -54 μM to 315 μM (n=19 evaluable, mean baseline CST 373 μM).
Reductions in sub-retinal fluid from baseline at week 12 were also observed in patients treated with combination OPT-302 + Lucentis.
In treatment naïve patients, mean SRF was reduced by 125 μM (83 per cent), with 13/18 (72 per cent) patients having complete (100 per cent) resolution (n=18, baseline 142 μM). In those patients showing a sub-optimal response to prior ant-VEGF-A therapy, mean SRF decreased by 51 per cent (-62 μM), with 3/19 (16 per cent) patients having complete resolution of SRF and 9/19 (47 per cent) patients having a >50 per cent resolution of SRF at week 12 compared to baseline (n=19 evaluable, baseline 122 μM).