CicloMed’s lead drug development project targets bladder cancer

The first product in CicloMed’s drug development pipeline, Fosciclopirox, holds promise as a novel new agent targeting non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Bladder cancer is a disease with serious unmet need, as patients often endure a lifetime of monitoring, surgical procedures, immunotherapy and chemotherapy treatments.

Preclinical studies have indicated that Fosciclopirox, also known as Ciclopirox Prodrug or CPX-POM, exhibits activity against human bladder cancer cell lines (muscle-invasive and non-muscle invasive), as well as in a murine model of bladder cancer. Fosciclopirox is currently being evaluated in Phase 1 clinical studies under FDA-cleared protocols.

The drug candidate

Fosciclopirox is a patented compound that is rapidly and completely metabolized in blood to its active metabolite, Ciclopirox, which has been marketed as the active pharmaceutical ingredient in topical antifungal drug products since 1982. Ciclopirox has been demonstrated to act as an anticancer agent in vitro and in vivo, in part by inhibiting the Notch signaling pathway via inhibition of the gamma-secretase complex. Overexpression of the Notch signaling pathway has been associated with progression from non-muscle invasive to muscle invasive bladder cancer.

However, Ciclopirox itself has limited utility as an anticancer agent due to poor oral bioavailability and poor water solubility. As a prodrug, Fosciclopirox overcomes these development challenges and selectively delivers Ciclopirox to the entire urinary tract following intravenous or subcutaneous administration.

Discovered by a multidisciplinary team of researchers at The University of Kansas Cancer Center's Institute for Advancing Medical Innovation, Fosciclopirox was licensed to CicloMed LLC in November 2015 as part of a unique public-private partnership to take promising anticancer agents discovered at this NCI Cancer Center from “bench to bedside” – from laboratory research to clinical trials.

Clinical trials

Partnering with The University of Kansas Cancer Center, Cmed and Sarah Cannon Research Institute, CicloMed completed a first-in-human Phase 1 study in 2019 characterizing the safety, dose tolerance, pharmacokinetics and pharmacodynamics of Fosciclopirox in 19 patients with advanced solid tumors. The study also identified the Recommended Phase 2 Dose (RP2D).

A Phase 1 expansion cohort study of Fosciclopirox is underway now at two U.S. sites in cisplatin-ineligible muscle-invasive bladder cancer (MIBC) patients. This “window of opportunity” trial is characterizing the safety, dose tolerance, pharmacokinetics and pharmacodynamics of Fosciclopirox administered at the RP2D in 12 MIBC patients scheduled for cystectomy. 

For information on clinical trial eligibility and other details, please view the Phase 1 study’s disclosure page or search for CicloMed or CPX-POM on www.clinicaltrials.gov. 

Dr. Scott Weir & Dr. John Taylor discuss Ciclopirox Prodrug.