Roughly two years after raising $40 million in a private placement, Aerpio Pharmaceuticals’ lead experimental eye drug has hit a roadblock after failing a mid-stage study in patients with non-proliferative diabetic retinopathy (NPDR) — the earliest stage of diabetic eye disease, which occurs when high blood sugar levels cause damage to blood vessels in the retina.
These blood vessels can swell and leak, or close restricting blood flow and eventually culminate in blindness. In the 167-patient trial, called TIME-2b, patients were given the drug — AKB-9778 — (once or twice daily) or placebo (once or twice daily) for 48 weeks. The main goal was to improve the the study eye diabetic retinopathy severity score (DRSS) by two or more steps compared to the placebo.
Administration of AKB-9778 twice daily missed the study’s primary endpoint, the company said on Monday. Shares of the Cincinnati-based drug developer $ARPO cratered more than 68% to $1.36 in pre-market trading.
About 9.6% of patients given AKB-9779 twice daily experienced such an improvement, versus 3.8% on the placebo — drawing a less than rosy p value (p=0.270). The rates of progression to sight-threatening complications, including diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR), during the treatment period were similar between treatment groups, Aerpio noted, adding that the use of the experimental drug had an “encouraging” impact on key secondary goals, including a measure of kidney function and intraocular pressure.
Unlike patients with diabetic eye disease who are typically given anti-VEGF injections into the eye, AKB-9778 is self-administered subcutaneously by the patient, akin to insulin. The experimental drug is a small molecule inhibitor of VE-PTP, the most critical negative regulator of Tie2 — a pathway believed to stabilize vasculature — in diseased blood vessels. In a separate study, called TIME-2, AKB-9778 improved underlying symptoms by two or more steps on a diabetic retinopathy severity scale in both eyes.
Undeterred by the TIME-2b failure, Aerpio chief Stephen Hoffman expressed enthusiasm for the totality of data on the drug. “(C)ollectively these data support a potentially important role of the Tie2 pathway for the treatment of diabetic complications, as well as for open angle glaucoma,” he said in a statement, adding that a Phase Ib study of a topical drop formulation of AKB-9778 is expected to commence in the second quarter.
Aerpio also has another experimental eye drug in development, in addition to an investigational therapy for inflammatory bowel disease.
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