First Clinical Trial of Niclosamide-Based Metabolic Anticancer Drug Targets Hormone-Resistant Prostate Cancer

ADM Korea, a subsidiary of Hyundai Bioscience, has announced a significant step forward in the field of cancer treatment. On July 8, 2024, the company revealed the target population for its forthcoming clinical trial of a niclosamide-based metabolic anticancer drug. This groundbreaking trial will focus on prostate cancer patients who have developed resistance to hormone therapy.

The drug in question is designed to regulate the metabolic pathways of cancer cells, thus inducing their death. Importantly, it also blocks the signaling pathways that allow cancer cells to evade anticancer effects, thereby inhibiting drug resistance. This dual-action approach addresses a critical issue in cancer treatment: the ability of cancer cells to develop resistance to existing therapies over time.

Traditional anticancer treatments—including hormone therapies, chemotherapies, targeted therapies, and immunotherapies—often fail to overcome the problem of cancer cell resistance. This resistance occurs when cancer cells activate signaling pathways to evade the effects of repeated drug administration, diminishing the drugs' efficacy. Solving this problem has been a significant challenge in cancer treatment, and no existing drug has effectively addressed it.

Niclosamide has been identified as a potent inhibitor of the Wnt/β-catenin and STAT3 cell signaling pathways, which are linked to drug resistance in cancer cells. Studies have shown that when niclosamide is used in combination with other treatments—such as chemotherapies (SN38, azacitidine), immunotherapies (PD-L1 Ab), targeted therapies (erlotinib), and hormone therapies (enzalutamide)—the anticancer effects are significantly enhanced compared to single-agent treatments. However, its low absorption and short half-life have historically prevented its repurposing as an anticancer drug over the past six decades.

ADM Korea plans to overcome these challenges with a patented technology developed by CNPharm, another company involved in the project. This technology has successfully repurposed niclosamide as an oral metabolic anticancer drug. In a study involving a triple-negative breast cancer animal model, the combination of the chemotherapeutic agent docetaxel with the niclosamide-based drug showed a 67% improvement in anticancer effects compared to docetaxel alone. Additionally, a three-month animal toxicity study demonstrated that the drug's blood concentration at the NOAEL (No Observable Adverse Effect Level) was 7,888 ng/mL. In vitro studies further confirmed that cancer cell proliferation was reduced by 50% at concentrations well below the NOAEL, indicating the drug's safety.

ADM Korea has ambitious plans to initiate clinical trials combining the niclosamide-based drug with existing treatments for all terminal cancer patients who have developed resistance to current anticancer drugs. The company intends to submit an Investigational New Drug (IND) application to the Ministry of Food and Drug Safety of the Republic of Korea in August. The first clinical trial will focus on combining hormone therapy with the niclosamide-based drug for prostate cancer patients resistant to hormone therapy.

The decision to target prostate cancer patients first is based on several factors: the increasing number of such patients, the lack of effective treatments for those resistant to hormone therapy, the relatively shorter clinical trial period for prostate cancer (around four weeks), and the potential for higher therapeutic effects compared to other cancers.

A recent paper in The Lancet predicts that the global number of prostate cancer patients will more than double from 1.4 million in 2020 to 2.9 million by 2040. The global market for prostate cancer treatment is expected to reach approximately 29.8 trillion KRW by 2025. Combining niclosamide with existing treatments is anticipated to significantly enhance the effectiveness of anticancer therapies and improve the quality of life for cancer patients.

ADM Korea's Vice President, Jin Geun-woo, emphasized the importance of the upcoming clinical trial. The trial aims to verify the safety and efficacy of combining the niclosamide-based metabolic anticancer drug with hormone therapy in prostate cancer patients over a four-week period, monitored by PSA levels. Previous studies have shown that niclosamide, when combined with enzalutamide, can reduce tumors by approximately 72%, compared to just 5% with enzalutamide alone. This new drug could mark a historic turning point in the treatment of prostate cancer.