Quark Pharmaceuticals announced successful completion of a randomized, double-blinded, placebo-controlled multicenter Phase 2 trial of QPI-1002, a synthetic chemically modified siRNA acting to temporarily reduce p53 expression, for the prophylaxis of acute kidney injury (AKI) following cardiac surgery (QRK-209; NCT02610283).
The study included 341 subjects of age 45 or greater undergoing cardiac surgery and at risk for AKI, randomized in a 1:1 ratio to QPI-1002 or placebo. The primary endpoint for the study, the proportion of subjects developing AKI through Day 5, based on the Acute Kidney Injury Network (AKIN) classification, was achieved, with QPI-1002 treatment significantly reducing the incidence of AKI.
The QPI-1002 treatment effect observed in the overall study population was consistent in predefined subgroups of subjects including those with chronic kidney disease (CKD), diabetes, and high-risk patients who underwent multiple cardiovascular surgical procedures. A statistically significant treatment effect was also seen for AKI defined by the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification.
QPI-1002 appeared to be well tolerated in the study. QPI-1002 had similar rates of adverse events compared to placebo, with the most common events occurring in both treatment groups being those typically seen following cardiovascular surgery including pleural effusions, respiratory and infectious complications.
These trial findings support continued development of QPI-1002 for the prevention and amelioration of AKI associated with cardiac surgery in patients at risk for whom no approved therapy exists to date. Quark believes that QRK-209 study, enrolling hundreds of patients, is the first well-controlled clinical trial to achieve the primary endpoint of reduction of AKI. The data from this study will be submitted for presentation at an upcoming medical congress.
“Quark is developing QPI-1002 in a variety of indications associated with ischemia-reperfusion renal injury,” stated Dr. Shai Erlich, CMO and President Quark US Operations. “We are excited about the QRK-209 study results which reinforce the positive effect of QPI-1002 as previously reported in a randomized, double-blind, placebo-controlled multicenter Phase 2 study (QRK-006b; NCT00802347) where QPI-1002 was shown to reduce the incidence and severity of delayed graft function (DGF) in patients undergoing renal transplantation. The results of these two studies validate Quark’s vertically integrated Discovery-to-Development Platform and supports Quark as a leader in the field of siRNA therapeutics. QPI-1002 is currently being evaluated in a Phase 3 clinical study (QRK-306; NCT02610296) for the reduction of DGF incidence and severity.”
“AKI is one of the major complications following cardiac surgery and is associated with increased hospitalization, development of chronic kidney disease and higher post-surgical mortality. There is currently no approved treatment for the prevention of AKI,” observed Dr. Bruce A. Molitoris, Distinguished Professor of Medicine and Cellular and Integrative Physiology Indiana University School of Medicine and past president of the American Society of Nephrology. “The results of the Quark QRK-209 study are encouraging and bring us closer to having a treatment that would reduce AKI incidence which represents a significant advance in patient care.”
Filed Under: Drug Discovery