Australian company Opthea Limited said it has successfully completed end-of-phase-2 meetings with the US Food and Drug Administration (FDA) and a Scientific Advice meeting with the European Medicines Agency (EMA), to clear the way for 2 large pivotal phase 3 clinical trials for “pan-VEGF” OPT-302 as a treatment for wet AMD. The company is on-track to initiate the two 900-patient phase 3 trials as complementary therapy to aflibercept (Eylea; Regeneron) and ranibizumab (Lucentis; Genentech) in early 2021. Both Eylea and Lucentis combat VEGF-A, while OPT-302 attacks VEGF-C and VEGF-D.

The FDA and EMA agreed on key aspects of the proposed phase 3 clinical trial designs, including the conduct of 2 concurrent, global, multicenter, randomized, sham-controlled studies evaluating OPT-302 in combination with Lucentis, a trial referred to as ShORe, or Eylea, a trial referred to as COAST. If successful, the investigation of OPT-302 in combination with 2 approved standard of care VEGF-A inhibitors could enable OPT-302 to be administered with either Eylea or Lucentis.

Moreover, each trial will compare the clinical efficacy of OPT-302 administered in combination with a VEGF-A inhibitor on an every 4-week and every 8-week dosing regimen to understand the durability of OPT-302 treatment effect with less frequent dosing. The primary endpoint is mean change in visual acuity from baseline to week 52 for OPT-302 and anti-VEGF-A combination therapy compared to anti-VEGF-A monotherapy, with the company intending to submit Biologics License and Marketing Authorization Applications with the FDA and EMA, respectively, following completion of this primary efficacy phase of the trials. Each patient will continue to be treated for a further year to evaluate safety and tolerability over a 2-year period.

The 2 OPT-302 phase 3 trials build upon and maintain key features for consistency with the company’s positive phase 2b clinical trial of OPT-302, while evaluating the administration of OPT-302 combination therapy over a longer treatment period and in a greater number of patients. In addition, the phase 3 trials are optimized based on phase 2b outcomes to maximize probability of success and commercial opportunity. Analysis of the phase 2b trial demonstrated that OPT-302 combination therapy increased visual acuity by a further +5.7 letters over Lucentis monotherapy in wet AMD patients with minimally classic and occult lesions, representing the majority (~80%) of wet AMD patients.