Positive preliminary results from wet AMD trial

Opthea (ASX:OPT) has announced positive data from its ongoing first-in-human clinical trial of OPT-302, a VEGF-C/D ‘Trap’ therapy for wet age-related macular degeneration (wet AMD), causing the company’s share prices to jump by over 20% today.

The study is being run under an Investigational New Drug (IND) program with the FDA at 14 sites across the US. It comprises two parts: a sequential dose escalation (Phase 1, 20 patients) and a randomised dose expansion study (Phase 2A, up to ~30 patients) in patients that have either not been treated previously (treatment naïve patients) or who have demonstrated a suboptimal response to prior anti-VEGF-A therapy.

The Phase 1 dose escalation enrolled 20 patients into three OPT-302 dose level groups (0.3, 1 or 2 mg) in combination with Lucentis (0.5 mg) and an OPT-302 monotherapy group (2 mg). The study met its primary objective, with OPT-302 demonstrating safety and tolerability both as monotherapy and in combination with Lucentis. No dose-limiting toxicities and no treatment-related serious adverse events were observed through week 12 of the study.

Secondary endpoints demonstrated encouraging clinical activity of OPT-302 in both treatment of naïve patients and those who showed a suboptimal response to prior anti-VEGFA therapy. A majority of patients (16/19 evaluable at week 12) maintained or gained vision by week 12 compared to baseline, while the other three patients did not lose more than three letters.

The mean gain in visual acuity overall from baseline at week 12 in treatment naïve patients who received OPT-302 + Lucentis was 16.5 letters and 9.5 letters in the 2 mg OPT-302 + Lucentis dose cohort. The mean visual acuity gain from baseline at week 12 in patients who showed a suboptimal response to prior anti-VEGF-A therapy was four letters with OPT-302 + Lucentis.

The mean central subfield thickness (CST), a measure of the average retinal thickness at the centre of the retina, decreased in all OPT-302 + Lucentis treatment groups at week 12, with a mean reduction from baseline of 214 µM (42.7%) in treatment-naïve patients and 42 µM (10.8%) in patients who showed a suboptimal response to prior anti-VEGF-A therapy.

In the OPT-302 monotherapy cohort, 3/5 patients did not require rescue with anti-VEGF-A therapy. At week 12, in patients that did not undergo rescue, there was a mean visual acuity gain of 3.3 letters from baseline and a mean increase in CST of 18 µM.

“Combination therapy with OPT-302 and standard of care Lucentis is both feasible and well tolerated in patients who are either naïve to treatment or resistant to prior therapy,” stated Dr Pravin Dugel, a member of Opthea’s clinical advisory board. “Although the preliminary clinical activity data to date is based on a small number of patients, the promising gains in vision and anatomic improvements on SD-OCT that have been observed suggest that combined inhibition of VEGF-C/D and VEGF-A may lead to improved outcomes over Lucentis alone.

“While we expect that the OPT-302 data will continue to evolve as more patients are enrolled in the Phase 2A trial, the early evidence of an additive benefit of OPT-302 observed in this study is very promising and warrants further investigation of OPT-302 in a large randomised controlled clinical study in wet AMD patients.”

Opthea (ASX:OPT) shares were trading 21.67% higher at $0.645 as of around 12 noon on Tuesday.