A bladder cancer drug discovered and developed at The University of Kansas Cancer Center is set to become its first cancer drug to go from bench to bedside.
KU Cancer Center's nationally recognized proof-of-concept center and product development arm, the Institute for Advancing Medical Innovation (IAMI), translates laboratory and bedside discoveries into new drugs, diagnostic tests and medical devices with the goal of advancing promising medical innovations to patients. Simply put, IAMI works with KU Cancer Center and other National Cancer Institute-designated centers to develop medical innovations that change the standard of cancer care. Through a research effort led by IAMI, patients with bladder cancer may finally have a new treatment option. More than two decades have passed since a new therapy has been introduced.
Bladder cancer is the fifth most common cancer in the United States, with approximately 77,000 new cases and 16,000 deaths annually. It has the highest recurrence rate among all cancers - up to 50 percent of cases may recur within 12 months. Additionally, 25 percent may advance to muscle invasive disease, requiring more aggressive treatment. As such, patients face a lifetime of monitoring and medical care.
Standard care for non-muscle invasive disease is surgical removal of the tumor and possible administration of chemotherapy or immunotherapy directly into the bladder. While effective for most patients, some cases may not respond, develop intolerance, or recur during treatment.
Giving an old drug a new purpose
Ciclopirox was first marketed in 1982 as an antifungal agent found in several topical drug products. KU Cancer Center researchers began working on ciclopirox through a collaboration with The Leukemia and Lymphoma Society and Ontario Cancer Institute as a potential treatment for acute myeloid leukemia (AML). However, a clinical trial demonstrated that ciclopirox, given orally, was not a viable treatment.
Researchers Scott Weir, Pharm.D., Ph.D., director of IAMI, and Shrikant Anant, Ph.D., associate director for cancer prevention and control research program, decided to modify the drug to be administered intravenously. The new drug, called Ciclopirox Prodrug, converted to ciclopirox in the bloodstream where it then was selectively delivered to the urinary tract. Further research demonstrated that it was able to kill bladder cancer cells.
Following these promising findings, Anant and Weir recruited renowned bladder cancer expert John Taylor III, M.D., MS, professor of urology at the University of Kansas School of Medicine, whose lab has extensive experience in bladder cancer modeling, as well as the ideal mouse model in which to test the drug.
"Fantastic results. Not only did the drug have an effect on the cancer cells, but it did not harm surrounding healthy cells," Anant said.
Anant, Taylor and Weir demonstrated in animals that giving Ciclopirox Prodrug by injection selectively delivers the active anticancer agent, ciclopirox, to the entire urinary tract. At well tolerated doses administered intravenously and by injection, urinary tract concentrations of the active agent are achieved that exceed those required to kill bladder cancer cells in the test tube by severalfold.
"This is potentially a game-changer in treating patients with non-invasive bladder cancer. A new and effective drug, which doesn't require catheterization, is welcomed in a field where care has not advanced much in several decades," Taylor said.
Because the Food and Drug Administration (FDA) requires extensive resources to demonstrate that a drug is a viable treatment for patients, academic institutions often partner with the private sector to advance the drug to a clinical trial. Under an existing partnership agreement, the University of Kansas Medical Center licensed Ciclopirox Prodrug to BioNovus Innovations LLS. Development is being managed by BioNovus subsidiary CicloMed LLC. This is the first product development and commercialization collaboration between BioNovus and IAMI.
CicloMed is on track to submit an investigational new drug (IND) application to the FDA in early 2017. Pending FDA clearance, the firm intends to initiate a Phase I clinical trial at several sites, including KU Cancer Center. The goal is to enroll the first patient in a clinical trial by mid-2017.
"It takes a village to understand the biology of cancer, discover and develop new cancer treatments and demonstrate that the treatment is effective," Weir said. "We're proud to have built a team of experts whose strengths span the spectrum of research - from basic to translational to clinical. Because of this team effort, bladder cancer patients may soon have better treatment options."