April 27, 2018
By Greg Peters
A drug with a decades-long history of research and testing at the University of Kansas Medical Center has been approved by the Food and Drug Administration as the first treatment for autosomal dominant polycystic kidney disease, the most common form of PKD.
The two forms of PKD - autosomal dominant (ADPKD) and autosomal recessive (ARPKD) - affect 600,000 people in the United States and millions worldwide. Earlier this week, the FDA approved the use of tolvaptan, a targeted treatment that has shown it can slow the growth of cysts on the kidney and the progression of the disease. While not a cure, it is a significant breakthrough in the treatment of PKD.
"This is an incredible bench to bedside story," said Alan Yu, M.B., B. Chir., professor and director of the Jared Grantham Kidney Institute at the University of Kansas Medical Center. "This is the aspiration of all of us here to be able to do science that develops a completely new treatment that can then be translated to the bedside; tested in patients; and shown to be effective. So this is something we're all extremely proud of."
ADPKD, the fourth-leading cause of end-stage renal disease, is a condition in which fluid-filled cysts develop within the kidneys and enlarge the organs. The progressively debilitating genetic disease is often painful and impairs normal kidney function in many patients resulting in kidney failure. Patients taking tolvaptan twice a day should experience an extended period before they need dialysis or a transplant, according to the Japanese drug manufacturer Otsuka Pharmaceutical Co. Ltd., which markets the drug under the name JYNARQUETM. The PKD Foundation says on its website that JYNARQUE TM should be available by early June. Jynarque originally was approved by the FDA in 2009 for the treatment of hyponatremia.
"This breakthrough will give hope to patients that something positive can be done now to slow their disease progression, and that other family members who are at risk for the disease will have the option of a treatment in the future, if and when that time comes," said James Calvet, Ph.D., a professor in the Department of Biochemistry and Molecular Biology and part of the Grantham Kidney Institute.
The late Jared Grantham, M.D., co-founder of the PKD Foundation and former director of the kidney institute that bears his name at the University of Kansas Medical Center, was a pioneer in PKD research and began studying PKD mechanisms in the 1970s. In 2012, he co-authored a paper in the New England Journal of Medicine based on a three-year international study showing tolvaptan to be an effective treatment for kidney disease,"Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes."
Many participants at KU Medical Center were included in the trial, which was monitored by Franz Winklhofer, M.D. KU Medical Center faculty members including Calvet, Vincent Gattone, Ph.D. (later at Indiana University), Darren Wallace, Ph.D., Robin Maser Ph.D. and Professor Emeritus Lawrence Sullivan, Ph.D., all had important roles in advancing the research.
"I think Dr. Grantham would be over the moon," Yu said of the FDA approval. "This is something he'd been waiting a long time for."
"Jared would have been thrilled that his decades-long dream to find a cure that he was so passionate about and involved so many researchers and patients worldwide became a reality," Calvet said. "He would have been very happy for the patients. He also would have been sanguine, knowing that there is a lot more to do and optimistic that newer, better therapies will be found."