Early Combination Therapy Results Show Efficacy for Diabetic Macular Edema

July 28, 2020
Kenny Walter

In a phase 1b study presented virtually during ASRS 2020, investigators found a reduction in central subfield thickness after 12 weeks of OPT-302 combined with aflibercept injections.

Early phase results show a combination of OPT-302 and aflibercept could be beneficial to patients suffering from diabetic macular edema (DME).

In findings presented at the American Society of Retina Specialists 2020 (ASRS 2020) Virtual Sessions, a team, led by David S. Boyer, MD, evaluated the safety, visual function, and anatomic outcomes of switching patients with persistent diabetic macular edema from anti-VEGF-A monotherapy to combination therapy of OPT-302 with aflibercept.

OPT-302 inhibits VEGF-C/-D and could contribute to treatment resistance with VEGF-A suppression.

In the phase 1B study, the investigators examined patients receiving escalating doses of OPT-302 (0.3, 1 or 2 mg) with aflibercept (2mg) in 3 separate cohorts. Next, in a phase 2a study, the investigators will examine about 108 patients randomized to either aflibercept with OPT-302 (2mg) or aflibercept alone.

Each patient received intravitreal injections of aflibercept with OPT-302 once every 4 weeks over the course of 12 weeks. They were then followed an additional 12 weeks, where aflibercept retreatment was available as needed if there was at least a 5 letter decline in best-corrected visual acuity (BCVA) or at least a 10% increase in retinal thickness.

The investigators sought several outcomes, including safety, the effects on BCVA, and anatomical changes.

In the interim analysis from the preceding phase 1b dose escalation study, the investigators examined 9 patients with a mean injections of prior anti-VEGF-A monotherapy of 6.3. The last one was given a mean 36 days prior to switching to combination therapy.

They found that multiple dosing of IVT aflibercept with OPT-302 was well tolerated at all 3 dosing levels with no dose limiting toxicities.

For the whole group analysis, the mean change in BCVA at week 12 increased by 7.7 letters (95% CI, 2-13.3) from baseline (65 letters). A dose response relationship of improved BCVA was also observed with increasing doses OPT-302 combined with aflibercept.

The group also found a reduction in central subfield thickness at week 12 of -71µm (95% CI, -117 to -26) from baseline (434 µm) and 6 of 9 (67%) patients had at least a 50% reduction in excess foveal thickness as measured on SD-OCT.

“Conversion to combination OPT-302 with aflibercept was well tolerated with improved visual and anatomic outcomes in patients with persistent DME despite prior anti-VEGF-A monotherapy,” the authors wrote. “Thus, dual-targeted inhibition of VEGF-C/-D and VEGF-A may hold promise in the management of DME.”

In another study presented at ASRS 2020, investigators suggest new methods to improving long-term visual outcomes in eyes with diabetic macular edema are needed.

The team assessed routine clinical care practices for participants. They retrospectively collected data on clinical visits and retina treatments in the study eye occurring between the two- and five-year extension period.

The primary objective for the 3 years after Protocol T was stopped was to provide information on treatment course, visual acuity, and diabetic macular edema. The main objective did not include comparing treatment groups after 2 years, Pieramici said during the presentation of his research team’s data and findings.

The study, “Switching to Combination OPT-302 With Aflibercept From Prior Anti-VEGF-A Monotherapy in Eyes With Persistent Diabetic Macula Edema (DME),” was published online by ASRS 2020.