BURLINGTON, Mass.—New clinical data suggest that a novel therapy under development by AlloCure could offer effective treatment for patients suffering from acute kidney injury (AKI).
In a 16-subject, Phase 1 clinical trial, the AlloCure therapy, AC607, appeared safe and well tolerated. Furthermore, treated subjects experienced a lower incidence of AKI, reduced length of hospital stay, and reduced hospital readmission rates compared to a cohort of historical controls.
The study was presented on November 12 at the American Society of Nephrology annual meeting held in Philadelphia.
“AKI represents a significant unmet medical need and is experienced by approximately 1 million patients each year in the United States, with profound consequences including extended hospitalization, the need for dialysis, and death,” said David Warnock, MD, the Hilda B. Anderson Endowed Chair in Nephrology at the University of Alabama at Birmingham. “At present, there are no effective therapies to treat AKI other than supportive measures.”
AC607 is a novel biologic therapy under development for AKI. AC607 is comprised of adult bone marrow-derived mesenchymal stem cells. AC607 homes to the injured kidney where it mediates an anti-inflammatory, organ repair process. Importantly, AC607 is not recognized by the immune system, enabling its use in an “off the shelf” paradigm without the need for blood or tissue typing.
Robert M. Brenner, MD, AlloCure President and CEO said, “We are very encouraged with these initial clinical trial results for AC607 in patients who were at high risk of AKI, and we look forward to expanding on these results with a Phase 2 trial that is scheduled to begin in 2012.”
Study Design and Results
The Phase 1 trial of AC607 treated 16 subjects who underwent coronary artery bypass grafting (CABG) and/or heart valve surgery and who were at high risk for developing AKI. At baseline, 15 subjects had chronic kidney disease, 13 were hypertensive, and 6 had diabetes. The primary endpoint for the study was safety; none of the study subjects experienced severe adverse events attributable to AC607 treatment.
To enable a preliminary assessment of efficacy, trial subjects were matched to a cohort of historical controls from the same institution where the Phase 1 study was conducted. Subjects were matched according to sex, race/ethnicity, co-morbid conditions, and other risk factors for AKI. Just 2 of 16 (12.5%) AC607-treated subjects developed AKI (using the Acute Kidney Injury Network [AKIN] criteria) compared to 19 of 64 (29.7%) of the historical controls. Hospital length of stay was significantly reduced in the AC607-treated subjects compared to historical controls [6.5 ± 3.1 days vs. 9.3 ± 5.4 days, respectively (p =0.049)]. Hospital readmission rates were 6.3% vs. 12.5% for AC607-treated subjects and historical controls, respectively. One subject died within 30 days of surgery in the treated group (unrelated to AC607) vs. 2 in the historical control group. No subjects in either group received dialysis.
Epidemiological Study of AKI
On November 10 at the ASN annual meeting, AlloCure and Outcomes Insights presented an epidemiological study of cardiac surgery patients which evaluated different definitions of AKI and determined the risk of death, dialysis, time to kidney recovery, and duration of hospital stay. The study analyzed data from 33,249 patients collected from 53 U.S. hospitals. The study found that patients who developed AKI within 24 hours after surgery were at greater risk of in-hospital death and dialysis (10.3% and 3.5% respectively), than those who developed AKI between 25 – 48 hours after surgery (5.3% and 2.2% respectively). Across the 24-hour definitions, patients with a 100% rise in serum creatinine were at the greatest risk for death and dialysis (31.5% and 5.0%, respectively); the number of patients who met this threshold was 1% of the population. Patients with a 0.5 mg/dL rise (approximately 5% of the total study population) in serum creatinine within 24 hours of surgery had worse outcomes compared to patients with a 0.3 mg/dL rise within the same timeframe (16.0% death and 6.2% dialysis vs. 10.3% death and 3.5% dialysis, respectively).
Glenn Chertow, MD, the Norman S. Coplon/Satellite Healthcare Professor of Medicine and Chief, Division of Nephrology at Stanford University School of Medicine commented that, "These findings provide new insights regarding the association of clinical outcomes in patients meeting different definitions of AKI following cardiac surgery. Importantly, these findings can help to inform the design of prospective clinical trials for the treatment of AKI in this population.”