Australian company Opthea (ASX:OPT) has announced topline results from its phase 2a trial evaluating the safety and efficacy of its biologic OPT-302 administered with Bayer's PBS-listed EYLEA (aflibercept) in treatment-refractory patients with persistent diabetic macula edema (DME).
The company said the trial met the prespecified primary efficacy endpoint with 52.8 per cent of patients achieving ≥ five letters gain in 'Best Corrected Visual Acuity' (BCVA) at week 12.
It said the co-primary endpoint of safety was also met with 2.0 mg OPT-302 in combination with 2.0 mg EYLEA being well tolerated with a similar safety profile to control group.
“These Phase 2a data are very promising given that dual-targeted inhibition of VEGF-C/-D and VEGF-A with OPT-302 combination therapy demonstrated biological activity across multiple vision and anatomical endpoints which may lead to improved outcomes in the management of DME,” said Dr David Boyer, Senior Partner Retina Vitreous Associates Medical Group in Los Angeles and Clinical Professor at the University of Southern California Roski Eye Institute.
Dr Boyer, who is a study investigator on the trial, continued, “These results show the potential of OPT-302 combination therapy for people living with diabetic macular edema, a leading cause of vision loss in working-age adults.
"With limited treatment options currently available and many patients who do not adequately respond to anti-VEGF-A therapies, there remains a significant unmet need for more efficacious and durable therapies for DME. If we could add a treatment such as OPT-302 to potentially improve vision in this population of hard to treat patients, this would be significant.”
The Phase 2a trial is a randomised, double-masked, sham-controlled, proof-of-concept clinical trial conducted at 53 sites in the US, Israel, Australia and Latvia.
The trial recruited a total of 144 participants, with 115 of the 144 patients conforming sufficiently with the trial protocol and included in the 'Per Protocol' population. The company said all participants enrolled in the trial were diagnosed with persistent DME despite regular intravitreal administration of prior anti-VEGF-A monotherapy.
The company said mean change in BCVA at week 12 compared to baseline was 5.9 letters for OPT-302-EYLEA combination therapy and was similar in the Eylea control group at 6.1 letters. It said 52 per cent of patients in the OPT-302 combination and 60 per cent of patients in the Eylea control group gained ≥five letters. However, a higher proportion of patients gained ≥10 and ≥15 letters of vision following the OPT-302-EYLEA combination (26.7 per cent) compared to the control group (22.5 per cent). In addition, 12 per cent of patients in the OPT-302-EYLEA combination group and 7.5 per cent of patients in the EYLEA control group had ≥15 letter gains respectively.
The company reported an exploratory subgroup analysis of patients with prior treatment with monotherapy EYLEA. It found these patients treated with the OPT-302-EYLEA combination recorded a mean change in BCVA at week 12 compared to the baseline of 8.6 letters - it was 5 letters in patients who continued on EYLEA monotherapy.
It said the proportion of patients in the subgroup gaining ≥10 and ≥15 letters from baseline to week 12 was 50 per cent and 16.7 per cent in the OPT-302-EYLEA combination group compared 0 per cent for both parameters in the EYLEA control.
“We believe that the results of this Phase 2a DME trial, together with the positive outcomes of the Company’s Phase 2b trial with OPT-302 in wet AMD, further validate Opthea’s approach to target VEGFC and VEGF-D to address the substantial unmet medical need for patients with these retinal eye diseases despite the availability of selective inhibitors of VEGF-A,” said Dr Arshad Khanani, Director of Clinical Research at Sierra Eye Associates in Reno, and study investigator on the trial.
“I am very encouraged and hopeful for the potential of OPT-302 combination therapy to provide physicians with further treatment options for our patients. The well-tolerated safety profile that we have consistently observed with this molecule is encouraging and the biological activity observed in this trial, in patients that are very difficult to treat and with different prior-treatment histories, bodes well for the further clinical development of OPT-302,” added Dr Khanani.
This Phase 2a trial is ongoing with the final participants due to complete the long-term week 24 follow-up visit later this month. It is anticipated that additional exploratory analyses and the final outcomes for longer term safety and treatment durability will be available in the second half of calendar year 2020.
“These positive topline Phase 2a results in a second disease indication of DME, build on our extensive prior clinical studies in wet AMD which demonstrated superiority in visual improvement with OPT-302 combination therapy compared to anti-VEGF-A monotherapy standard of care," said Dr Megan Baldwin, CEO and Managing Director of Opthea.