Opthea's Lucentis/VEGF 'trap' combo outshines Lucentis alone in wet AMD

Roche, Novartis, Regeneron and Bayer have made blockbusters of their anti-VEGF eye meds—the first two companies market Lucentis and the latter pair Eylea. But combining Lucentis with a new drug that targets different forms of VEGF could yield even better results in wet age-related macular degeneration (AMD), phase 2 data show. 

Wet AMD is caused by the growth of leaky blood vessels in the eye, which leads to scarring in the retina and the death of photoreceptors. Lucentis and Eylea combat this growth by inhibiting a VEGF protein called VEGF-A. Melbourne, Australia-based Opthea is working on a new drug that targets other VEGF proteins—VEGF-C and VEGF-D—for use in combination with VEGF-A drugs. Like Lucentis and Eylea, Opthea’s drug is injected directly into the eye. 

Opthea tested two doses of its drug, OPT-302, in combination with Lucentis in a 366-patient phase 2b study. Last month, it reported that the combo bested Lucentis at improving vision, as measured by Best Corrected Visual Acuity, or the best vision a person can achieve wearing glasses or contact lenses using a standardized eye chart. After 24 weeks, patients on the combination with the higher dose of OPT-302 could read an average of 14 letters more than they could before treatment, while patients on Lucentis alone read an average of 11 more letters.  

Now, at the European Society of Retina Specialists EURETINA 2019 Congress, Opthea is unveiling more data showing how the combination treatment affected the structure of the eye. 

The combo beat Lucentis at reducing the area of abnormal blood vessels in patients’ eyes by 38% and at cutting the total area of scarring by 39%. The study also looked at fluid that had leaked into the space under the retina, finding that fewer patients on the combo had subretinal fluid after 24 weeks compared to those taking Lucentis alone. 

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“Together with the previously reported superiority in visual acuity gains, the further data analyses support the primary outcome of the study and demonstrate that OPT-302 has direct mechanistic effects on wet AMD lesion pathology,” said Opthea CEO Megan Baldwin, Ph.D., in a statement. 

“These compelling results clearly support advancing OPT-302 into pivotal registrational Phase 3 development,” Baldwin said on a conference call last month. “We firmly believe that OPT-302, which was designed specifically for the eye as the first ‘trap’ inhibitor of VEGF-C and VEGF-D, which are part of the most validated target pathway in back of the eye diseases has considerable potential to improve outcomes in wet AMDand other retinal vascular diseases.” 

The company is also testing the drug with Eylea in diabetic macular edema, a consequence of diabetic retinopathy in which high blood sugar damages the retina’s blood vessels. Fluid builds up in the macula, which is in the center of the retina, making it swell and distorting vision. It expects topline data from a phase 2a study in early 2020. 

Opthea isn’t the only company seeking to improve upon today’s anti-VEGF meds, which can be unappealing to patients because they are injected into the eye. Kodiak Sciences is working on a drug that has a longer ocular half-life, meaning it sticks around in the eyes for longer, which would allow for patients to go longer between injections. The company reported data in July that the candidate, KSI-301, improved vision and reduced retinal thickening in patients with AMD, diabetic macular edema and macular edema stemming from retinal vein occlusion.