166Ho-Chitosan

Overview
¹⁶⁶Ho-Chitosan, also known as DW166-HC, is an innovative radiopharmaceutical drug designed for targeted cancer therapy. Commercially available under the brand name Milican in South Korea, it was developed by Dong Wha Pharmaceuticals and launched in August 2001. This therapeutic agent offers a novel approach for treating hepatocellular carcinoma (HCC), leveraging the unique properties of chitosan combined with holmium-166 (166Ho).

Clinical Applications
Chitosan, a biopolymer derived from chitin extracted from crab shells, exhibits distinctive behavior in varying pH conditions. In its gel form, it is stable at slightly acidic pH levels but solidifies into a foam-like structure when the pH drops below 7.0—conditions typically present near tumor cells. This transformation enables ¹⁶⁶Ho-Chitosan to localize and remain close to tumor sites, delivering targeted radiotherapy with minimal impact on surrounding healthy tissues.

The combination of chitosan and the radionuclide holmium-166 allows for efficient retention and effective therapeutic action against hepatocarcinoma cells. The first regulatory approval for this drug was granted for its application in treating hepatocellular carcinoma, making it a valuable addition to cancer therapy options.

Availability
Currently, ¹⁶⁶Ho-Chitosan is only available in South Korea, marketed as Milican Injection by Dong Wha Pharmaceuticals. The chitosan precursor used in its formulation is sourced from Norway, where it is manufactured under Good Manufacturing Practice (GMP) conditions to ensure quality and safety.

Potential for Broader Applications
While initially developed for hepatocellular carcinoma, research has explored the use of 166Ho-Chitosan in treating other conditions, including:

• Prostate cancer
• Glioblastoma (GBM)
• Rheumatoid arthritis (clinical trials for this indication were discontinued in 2005)

Dong Wha is also working on an innovative patch formulation for skin cancer, referred to as DW-167, which has successfully completed Phase II clinical trials.

Competitive Landscape
For small hepatocellular carcinomas (less than 3 cm), surgical intervention is the standard treatment. However, for larger tumors, radiopharmaceutical therapies are emerging as viable alternatives. Competing treatments include:

• ¹³¹I-Lipiodol (withdrawn from the market)
• ¹⁸⁸Re-HDD/Lipiodol (pending regulatory approval)
• Radioactive microspheres such as TheraSpheres and SIR-Spheres, which are classified as brachytherapy treatments.

In the field of glioblastoma treatment, competition is intense, with no product achieving full marketing authorization to date. Additionally, ¹⁶⁶Ho-Chitosan faces competition from other advanced local therapies, such as nanoparticles, implants, and treatments using alternative radionuclides like ¹⁷⁷Lu and alpha-emitters.

Despite this, holmium-166 exhibits a promising safety and efficacy profile, positioning ¹⁶⁶Ho-Chitosan as a compelling alternative for certain cancer indications.

Future Development and Challenges
While ¹⁶⁶Ho-Chitosan demonstrates strong potential, it must address key challenges to expand its reach beyond South Korea:

1. Limited Radionuclide Supply: Dong Wha relies on a single GMP-approved source of holmium-166. To support global expansion, securing a backup supply chain for the radionuclide is essential.
2. Generic Status: As a product with a longstanding history, ¹⁶⁶Ho-Chitosan is considered a generic drug, limiting its exclusivity. However, Dong Wha’s expertise and proprietary know-how in formulation and application present opportunities for innovation.

Further exploration into new indications—particularly those requiring localized radioactive treatments—could unlock additional therapeutic possibilities.

Conclusion
¹⁶⁶Ho-Chitosan represents a unique and effective approach to treating hepatocellular carcinoma and potentially other cancer types. Its localized action and biocompatible composition make it an attractive candidate for further clinical development. Despite its current limitations, including restricted availability and reliance on a single radionuclide source, strategic advancements could position this drug as a significant player in global radiopharmaceutical therapy.

By addressing its challenges and exploring untapped indications, ¹⁶⁶Ho-Chitosan has the potential to redefine localized cancer treatments.