Phase 2b wet AMD clinical trial

Opthea has completed a 366-patient Phase 2b clinical trial for the treatment of wet AMD in which OPT-302 administered in combination with the VEGF-A inhibitor Lucentis® (ranibizumab) demonstrated superiority in visual acuity gain compared to Lucentis® administered alone

“In testing for superiority against very intensive anti-VEGF-A therapy, the bar was set high. Despite this, OPT-302 (2.0 mg) combination therapy showed statistical superiority for the most accepted and sensitive primary efficacy outcome – mean visual acuity. Key secondary endpoints were very supportive of the primary outcome, and safety was favourable. Taken together, these results indicate that combined suppression of VEGF A, C and D has considerable potential as a novel treatment for wet AMD. OPT-302 may emerge as a combination treatment that can offer better vision gains than standard of care. Further registrational trials are clearly justified.”

Professor Tim Jackson, Consultant Ophthalmic Surgeon at King’s College London, Chief Investigator on the OPT-302-1002 study and member of Opthea’s Clinical Advisory Committee.

Phase 2b Wet AMD:
Clinical Trial Design

Opthea’s Phase 2b wet AMD clinical trial was a randomized, double-masked, sham-controlled study in 366 wet AMD patients at 109 sites across 10 countries.

The patients had not received any therapy for their newly diagnosed wet AMD (they were treatment-naïve). The trial investigated the clinical efficacy and safety of two doses of OPT-302 (0.5 mg and 2.0 mg) each in combination with Lucentis® (0.5 mg) and compared this to Lucentis® (0.5 mg) + sham injection.

Patients were randomised in a 1:1:1 ratio to each of the three treatment groups and treatments administered via sequential intravitreal (ocular) injection on a monthly basis for 6 months.

Further details on the Phase 2b trial can be found at www.clinicaltrials.gov, Clinical Trial Identifier: NCT03345082

OPT-302-1002 Clinical Trial Design: Phase 2b Study in Wet AMD (n=366)

The results of this clinical trial OPT-302-1002 were reported in August 2019 and presented at the European Society of Retina Specialists (EURETINA) Congress in Paris, France in September 2019.

Phase 2b Wet AMD:
Clinical Trial Results

The primary outcome measurement of the clinical trial was the mean change in best corrected visual acuity (BCVA) from baseline at week 24. This primary outcome was achieved with patients receiving the 2.0 mg OPT-302 combination therapy demonstrating superiority in visual acuity over patients receiving Lucentis® alone at week 24.

The 2.0 mg OPT-302 combination group gained a mean of 14.2 letters of vision from baseline at week 24, compared to 10.8 letters gained in the Lucentis® alone group, a statistically significant benefit of 3.4 letters (p=0.0107). This represents a greater than 30% relative improvement in vision outcomes in the OPT-302 combination group compared to ranibizumab monotherapy.

30% improvement in vision with OPT-302 combination therapy vs Lucentis®

Mean Gains in Visual Acuity From Baseline

Secondary outcome measurements from the study were also supportive of the primary outcome. In terms of improvement in vision, a higher proportion of patients in the 2.0 mg OPT-302 + Lucentis® group gained ≥10 and ≥15 letters compared to the Lucentis® alone group at week 24. In addition, fewer patients lost vision (assessed as losing ≥15 letters) at week 24 in the 2.0 mg OPT-302 + Lucentis® group compared to the Lucentis® alone group at week 24.

OPT-302 combination with Lucentis® improves vision gain & reduces vision loss

≥15 letter gain from baseline at week 24
≥15 letter loss from baseline at week 24

Secondary outcome measurements also demonstrated improvements in retinal anatomy supportive of the primary result of improvement in visual acuity. These secondary outcomes included reductions in central subfield thickness (CST), subretinal fluid and intraretinal fluid, and greater decreases in total lesion area and choroidal neovascularisation (CNV) area.

A number of pre-specified and exploratory analyses were also incorporated into the Phase 2b trial design in order to identify those wet AMD patients who may respond best to OPT-302. The Phase 2b trial randomized patients with a broad range of lesion morphologies including occult, minimally classic and predominantly classic lesions. Typically occult and minimally classic lesions do not respond as well to anti-VEGF-A therapy as predominantly classic lesions. In Opthea’s Phase2b trial, patients with occult and minimally classic lesions treated with OPT-302 combination therapy experienced greater improvement in visual acuity compared to ranibizumab alone. This suggests that greater activity of OPT-302 is observed in lesion-types considered more difficult to treat with anti-VEGF-A therapy and with the highest unmet need.

The Phase 2b clinical trial data confirmed the favorable tolerability profile of OPT-302. Opthea now has extensive global clinical dosing experience demonstrating a favorable tolerability profile following repeated intravitreal administration of OPT-302 in 399 patients, with over 1,800 doses of OTP-302 administered across three international clinical studies in two disease indications and in combination with the two leading standard of care anti-VEGF-A therapies, Lucentis® (ranibizumab) and Eylea® (aflibercept).

Overall, the results from these clinical trials with OTP-302 demonstrate potential to improve vision gains and reduce vision loss in patients with wet AMD.