Understanding Hepzato and Its Innovative Approach
Hepzato Kit combines the chemotherapy drug melphalan with a Hepatic Delivery System (HDS) for treating adults with uveal melanoma that has spread to the liver. The Hepzato Kit's innovation is its unique delivery method, percutaneous hepatic perfusion (PHP). This allows a higher concentration of chemotherapy in liver tumors than is safely possible with standard systemic chemotherapy, aiming to maximize effectiveness while reducing systemic side effects.
How the Hepzato Procedure Works
Percutaneous hepatic perfusion (PHP) using the Hepzato Kit is a minimally invasive procedure performed in a hospital by a specialized team. It involves three main steps:
- Isolation: Catheters and balloons are used to temporarily isolate the liver's blood supply.
- Saturation: Melphalan is infused into the hepatic artery for about 30 minutes, saturating the liver with a high dose.
- Filtration: Blood exiting the liver is filtered externally for about 30 minutes to remove chemotherapy before returning to circulation.
This targeted process distinguishes Hepzato from standard chemotherapy.
Indication, Eligibility, and Clinical Trial Data
Hepzato Kit was FDA-approved in August 2023 for adults with unresectable uveal melanoma liver metastases. Eligibility criteria are specific, requiring liver metastases to affect less than 50% of the liver and limited or treatable extrahepatic disease. The approval was based on the Phase 3 FOCUS trial, which showed an objective response rate of 36.3% in patients with hepatic-dominant metastatic uveal melanoma.
Comparing Hepzato (PHP) to Systemic Chemotherapy
| Feature | Hepzato (PHP) | Systemic Chemotherapy |
|---|---|---|
| Delivery Method | Minimally invasive procedure delivers drug directly to the hepatic artery. | Intravenous (IV) infusion distributes the drug throughout the entire body. |
| Target Area | High concentration of chemotherapy is confined to the liver. | Chemotherapy is circulated systemically, affecting both cancerous and healthy cells throughout the body. |
| Drug Dosage | High dose of melphalan is delivered to the liver due to isolated circulation. | Lower doses of chemotherapy are used to limit toxicity to healthy organs. |
| Systemic Exposure | Minimized by filtering the blood exiting the liver before it returns to circulation. | Widespread, leading to more significant side effects as the drug affects the whole body. |
| Side Effect Profile | More localized to the procedure and liver-related complications, with reduced systemic effects like severe nausea. | Higher risk of systemic side effects, including severe nausea, fatigue, and hair loss. |
Potential Side Effects and Management
Due to potential serious complications, Hepzato administration is restricted through an FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) program. The procedure requires close monitoring for at least 72 hours. Adverse reactions in the FOCUS trial were significant. Myelosuppression, including low blood cell counts, was the most common serious side effect. Peri-procedural risks include hemorrhage, liver injury, and blood clots. Gastrointestinal effects like nausea, vomiting, and abdominal pain are also common. Patients are screened for contraindications before treatment.
Conclusion
Hepzato offers a significant therapeutic option for patients with uveal melanoma metastatic to the liver, a population with limited treatment options. Using percutaneous hepatic perfusion, Hepzato delivers high-dose chemotherapy directly to liver tumors while reducing systemic side effects. Clinical trials have shown its effectiveness in shrinking tumors and potentially prolonging survival. However, its complex nature and risks mean it is administered to eligible patients under strict guidelines through a REMS program. Hepzato provides a powerful new tool against unresectable metastatic uveal melanoma in the liver.
For more detailed information on the FDA approval and clinical data, visit the official FDA announcement.
