Quark reached agreement with FDA on the overall Phase 3 trial design with a new innovative primary endpoint
Fremont, CA – July 9, 2018 – Quark Pharmaceuticals, Inc., a late clinical-stage pharmaceutical company and leader in the discovery and development of novel RNAi-based therapeutics for unmet medical needs, today announced the first patient dosed in the pivotal Phase 3 clinical trial of QPI-1002 a siRNA targeting p53, for the prevention of acute kidney injury (AKI) and its consequences following cardiac surgery (CS) (Trial QRK309, NCT03510897).
The Phase 3 trial is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of QPI-1002 in patients undergoing cardiac surgery. Eligible patients will be randomized to receive either a single dose of QPI-1002 by IV injection or placebo. The study will enroll approximately 1,038 subjects at high risk for AKI following cardiac surgery at 115 sites globally.
The primary endpoint of the QRK309 trial will be the proportion of subjects who develop any of the components of Major Adverse Kidney Events at Day 90 (MAKE90), defined as: Death through day 90, Initiation of Renal Replacement Therapy (RRT) through day 90, or an equal to or greater than 25% reduction in estimated glomerular filtration rate (eGFR based on serum cystatin C (eGFRcys) at the Day 90 visit. The traditional analyte for eGFR, a measure of renal function, is serum creatinine (SCr) which will also be assessed in the study in a sensitivity analysis for the primary endpoint.
In July 2017, Quark reported positive Phase 2 data from its large multicenter Phase 2 QRK209 (NCT02610283) clinical trial with QP-1002 for the prevention of AKI. In this trial, QPI-1002 demonstrated a 29% relative risk reduction in the MAKE90 endpoint (p=0.024) in the same patient population and same components of MAKE90 as in the primary endpoint of the current QRK309 Phase 3 trial. In addition, the Phase 2 study met its primary endpoint – it significantly reduced the incidence, severity and duration of AKI within the first five days of surgery in high risk patients (p = 0.0204) – as well as other multiple secondary endpoints.
“We are excited to announce the initiation of patient dosing in this Phase 3 trial with QPI-1002 using this important innovative endpoint which was designed based on our clinical Phase 2 data. This is an important milestone for Quark, building on our success from our Phase 2 study, towards enabling a potential new therapeutic option for cardiac surgery patients at high risk for developing AKI which is a serious complication of cardiac surgery and remains a major unmet medical need,” stated Dr. Elizabeth C. Squiers, Chief Medical Officer of Quark Pharmaceuticals, Inc.
“Moving forward with a Phase 3 trial with a new investigational product using this important MAKE90 endpoint based on Cystatin C, is an important advance in clinical trials for AKI,” stated Dr. Madhav Swaminathan Intensivist at Duke University Medical Center, Durham NC, one of the participating sites in the study. “Cystatin has been reported to potentially be a better way to estimate renal function in some patients at risk of renal deterioration” and as also recommended in the KDIGO guidelines. 
The same molecule QPI-1002 also completed dosing of 594 patients in a pivotal Phase 3 study (QRK306, NCT02610296) for delayed graft function (DGF) following kidney transplantation in January 2018. As in the AKI trial, the company reached agreement with the FDA on the overall Phase 3 trial design with a new innovative primary endpoint for DGF, based on the DGF Phase 2 data (QRK006, NCT00802347). We anticipate receiving the first interpretative results (FIR) in the fourth quarter of 2018.
More information can be found on QRK309 at or www.clinicaltrials.gov, identifier: NCT03510897
About Acute Kidney Injury (AKI)
In patients undergoing major cardiovascular surgery, post-surgical AKI develops within hours to days as a result of ischemic conditions caused by reduced local blood flow to the kidneys during surgery and reperfusion injury following restoration of the blood flow. Over 60% of cardiac surgery patients have moderate to high risk of AKI . 40% or more have AKI. The prognosis among patients requiring dialysis after cardiac surgery is poor, with an increased mortality risk exceeding 60% compared to the overall mortality rate of 2–8% after cardiac surgery. In patients who develop non-dialysis requiring AKI, the risk of short and long term mortality is increased up to 4- fold compared to patients with normal renal function after cardiac surgery . AKI is an unmet medical need, with no specific treatment available.
QPI-1002 is the first systemic siRNA drug to enter human clinical trials and to complete several well-controlled clinical studies with efficacy endpoints that were conducted in hundreds of patients. It is an investigational drug designed to temporarily inhibit the expression of the pro-apoptotic gene, p53, to protect normal cells from death stemming from acute tissue injury. Preclinical studies have shown that p53-targeted siRNAs can protect kidneys from ischemia-reperfusion injury in a variety of clinically relevant animal models. QPI-1002 has been granted Orphan Drug designation in the USA and Europe for prophylaxis of delayed graft function following kidney transplantation. Under an August 2010 agreement, Novartis has an exclusive worldwide license option for the development and commercialization of QPI-1002.
About Quark Pharmaceuticals, Inc.
Quark Pharmaceuticals, Inc. is a world leader in discovery and development of novel small interfering RNA, or siRNA, therapeutics for unmet medical needs. RNA interference is a biological process in which RNA molecules regulate expression of targeted genes. Quark’s fully integrated drug discovery and development platform spans the process from therapeutic target identification to drug development. Two products, QPI-1002 for delayed graft function (DGF) following kidney transplantation and QPI-1007 for non-arteritic ischemic optic neuropathy (NAION), have been granted orphan designation and are in global pivotal clinical studies. Quark’s broad pipeline of clinical and preclinical product candidates is generated from the company’s internally-developed siRNA platform technology and focuses on extrahepatic indications. Quark is headquartered in Fremont, California and operates research facilities in Ness-Ziona, Israel. For additional information please visit: www.quarkpharma.com.
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Quark Pharmaceuticals, Inc.
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