Results of a multicenter, double masked phase 2 clinical trial evaluating a small protein therapy (“abicipar”), for the treatment of diabetic macular edema (DME), indicates that the treatment may have functional and anatomical effects comparable to monthly treatments of ranibizumab. Presenting the data at last month’s AAO meeting in Chicago, Prof. Tarek S. Hassan, MD, Oakland University, reported on the results of a study conducted on a total of 151 patients with DME. The therapeutic treatment involved the delivery of a new class of molecules referred to as “DARPins”. DARPins, short for “designed ankyrin repeat proteins” are derived from natural ankyrin, or adaptor proteins, which are a common binding protein functioning in cell signaling and receptor binding acitivities. DARPins may be modified for highly specific target binding facilitating the specifc attack on a single validated disease pathway, limiting off-target effects. In addition, due to their small size, potentcy and stability, the molecules may have the potential to overcome some of the drawbacks found with other therapeutic approaches that can either be too large for effective penetration or too toxic in terms of side effects.
In the clinical study, 151 patients with DME (BCVA ≤75 and ≥24 letters) were randomized to receive abicipar 1mgQ8 (n=43), abicipar 2mgQ8 (n=42), abicipar 2mgQ12 (n=45) or ranibizumab 0.5mgQ4 (n=21) and all patients were followed for a period 28 weeks. In addition, all patients received doses at the start of the trial and at 4 and 8 weeks. According to Prof. Hassan, analysis of the primary endpoint indicateed that following 28 weeks of treatment, the mean change in BCVA from baseline was 7.2 letters for abicipar 2mgQ12, 7.1 letters for abicipar 2mgQ8, 4.9 letters for abicipar 1mgQ8, and 9.6 letters for ranibizumab. The secondary endpoint, mean change in central retinal thickness (CRT) from baseline, showed a change of -159.4 mm for abicipar 2mgQ12, -162.0 mm for abicipar 2mgQ8, -176.4 mm for abicipar 1mgQ8, and -158.8 mm for ranibizumab. According to a press realease of the results, the study was not powered to show statistically significant differences between treatment groups and, as such. the statistical and clinical significance of the study was not provided.
The trial did however report on common ocular adverse events which included vitreous floaters and conjunctival hemorrhage in the abicipar arms. Intraocular inflammation was reported to have occured in 7, 5 and 4 patients treated with abicipar 1Q8, 2Q8 and 2Q12 groups, respectively however, no such inflammation was reported within the ranibizumab treated group. According to the study sponsors, a company called Molecular Partners, based in Switzerland, the results were supportive of progressing to to a phase 3 study. Abicipar is understood to be a long-acting mono-DARPin drug candidate that inhibits vascular endothelial growth factor A (VEGF-A) and is currently under investigation for the treatment of both DME and wet age-related macular degeneration. The clinical rationale for the treatment is the potential to require less frequent injections into the eye than the current anti-VEGF therapies, while simulataneously providing equal or better improvements in vision.