Combination Treatment with Ranibizumab and AKB-9778 Shows Promise in Diabetic Macular Edema

Patients with diabetic macular edema (DME) are more likely to improve with treatment by a combination of ranibizumab and AKB-9778, as compared to treatment with either alone, concludes a study published in Ophthalmology. Another recent study touted the promise of intraocular anti-VEGF drugs like ranibizumab (and bevacizumab) at maintaining or even improving vision and reducing CST for patients with DME, but this study suggests a combination of older and newer treatment methods may yield even better results.

AKB-9778 is a small molecule, Tie-2 activating agent that effectively blocks vascular leak and pathologic angiogenesis in multiple disease conditions.

Approximately 150 subjects from 36 sites were studied; the first group received subcutaneous injections of 15 mg of AKB-9778 twice daily plus a monthly intraocular placebo injection, the second group received twice-daily placebo subcutaneous injections plus 0.3 mg of ranibizumab monthly, and the third group received both the 15 mg of AKB-9778 BID and the monthly 0.3 mg of ranibizumab.

Visual acuity and central subfield thickness (CST) were measured at the study’s outset, and then at four week intervals, for a total of 12 weeks. Secondary outcomes measured included the Diabetic Retinopathy Severity Score (DRSS).

At the study’s conclusion, CST improvement in the combination group was greater than either of the monotherapy groups (mean CST measurements at 12 weeks were -164.4±24.2 μm in the combination group, -110.4±17.2 μm in the ranibizumab group, and 6.2±13.0 μm in the AKB-9778 group). The same was true for visual acuity improvement: 56.2% of the combination group gained ≥10 letters (35.4% ≥10 letters, 20.8% ≥15 letters), as compared to 46.8% in the ranibizumab group (29.8% ≥10 letters, 17.0% ≥15 letters) and only 13% in the AKB-9778 group (8.7% ≥10 letters, 4.3% ≥15 letters). DRSS scores improved across all three groups, but with no significant differences between them.

Simply put, patients who received the combination of treatment methods were approximately 10% more likely to experience visual acuity improvement equal to or greater than 10 letters, as compared to those who received the anti-VEGF treatment alone; this suggests further investigation into whether promising anti-VEGF drugs may work best when prescribed in combination with another DME treatment method.