Aerpio Pharmaceuticals, a biopharmaceutical company focused on advancing first-in-class treatments for ocular diseases, has begun patient dosing in the company’s TIME-2b study, a phase 2b clinical trial designed to assess the efficacy and safety of Aerpio’s lead candidate AKB-9778 for patients with moderate to severe nonproliferative DR.

AKB-9778 is a small molecule, Tie2-activating agent that effectively blocks vascular leak and pathologic angiogenesis in multiple disease conditions, initially being studied for diabetic eye diseases. AKB-9778 has already proved promising in the earlier phase 2a TIME-2 study as a treatment for both DME and underlying DR. One arm of that study showed subcutaneous self-administered AKB-9778 to be effective in treating DME in combination with ranibizumab 0.3 mg (Lucentis; Genentech).

Because the study patients are all diabetics, most of them have experience doing their own subcutaneous insulin injections and were able to self-administer after very brief training.

The TIME-2b study is a double-masked, placebo-controlled, multicenter trial that will enroll 150 patients randomized 1:1:1 to receive either AKB-9778 15 mg subcutaneously once daily, AKB-9778 15 mg twice daily, or placebo for a 12-month period. The primary endpoint of the TIME-2b study is the percentage of patients who improve by at least 2 steps in diabetic retinopathy Severity Score (DRSS) in the study eye. Secondary objectives include assessment of safety and tolerability of both dosing regimens.

Victor H. Gonzalez, MD, of Valley Retina Institute in McAllen, Texas, who enrolled the first patient in TIME-2b, said in a press release, “TIME-2b is an exciting study because it allows us to evaluate a patient self-administered investigational drug for the treatment of moderate to severe nonproliferative diabetic retinopathy. An early treatment option that potentially improves diabetic retinopathy in both eyes without the need for intraocular injections could completely change our approach to diabetic eye disease.”

“The start of our TIME-2b study builds upon our clinical proof-of-concept data, for which we reported that AKB-9778 monotherapy was able to improve underlying diabetic retinopathy by 2 or more steps in DRSS in both eyes,” said Joseph Gardner, president and CEO of Aerpio in a press release. “Our goal with AKB-9778 is to treat early diabetic eye disease before the onset of these vision-threatening conditions.”

Paul A. Yates, MD, PhD, associate professor of ophthalmology and bioengineering at the University of Virginia, agrees there is a clear need for additional therapeutics beyond anti-VEGF to prevent progression of DR. "Targeting of the Tie2 pathway appears to be a rational approach based on both preclinical and early-stage clinical trials such as TIME-2," he said. "Toward that goal, it is promising that AKB-9778 treated patients demonstrated a trend toward improvement in DR severity score in TIME-2a. However, we will have to await the outcome of TIME-2b to know whether this effect is statistically significant."

In another, smaller study, Peter Campiocharo, MD, of the Wilmer Eye Institute, has completed a 16-patient, 84-day, phase 2a clinical trial using twice-daily, self-administered 15 mg AKB-9778 to treat macular edema associated with RVO (clinicaltrials.gov identifier NCT02387788).