In short
Marimastat is an investigational substance that belongs to a class of drugs called matrix metalloproteinase inhibitors. It was studied in a Phase 1 clinical trial involving 12 healthy volunteers to understand how the drug behaves in the body. Earlier research also explored its use in patients with unresectable cholangiocarcinoma, a type of bile duct cancer.
Key points
- Marimastat is a matrix metalloproteinase inhibitor, a type of drug that blocks enzymes involved in cancer spread.
- One Phase 1 trial studied a related product, PKL-021, in 12 healthy adults.
- The trial measured pharmacokinetics — how the drug is absorbed, distributed, and eliminated.
- The Phase 1 study was completed and also tested the effect of food on drug absorption.
- An earlier report described use of oral marimastat in four patients with unresectable cholangiocarcinoma.
What is marimastat?
Marimastat is an investigational substance classified as a matrix metalloproteinase inhibitor. Matrix metalloproteinases (MMPs) are enzymes that help cancer cells invade surrounding tissue and spread to other parts of the body. Marimastat was designed to block these enzymes. In the EU Clinical Trials Information System, the substance is recorded under the therapeutic area of nervous system diseases, which reflects the registry classification rather than its main studied use. The drug has been investigated primarily in oncology, particularly in cancers where tumour invasion is a concern.
How does marimastat work?
Marimastat works by inhibiting the activity of matrix metalloproteinases, enzymes that break down the extracellular matrix — the structural scaffold around cells. In cancer, tumour cells use MMPs to dissolve this scaffold, which allows them to invade nearby tissues and enter blood vessels to form metastases. By blocking these enzymes, marimastat aims to slow or prevent tumour invasion and spread. This mechanism is distinct from chemotherapy, which directly kills dividing cells.
Which conditions is marimastat used or studied for?
- Cholangiocarcinoma — a cancer of the bile ducts. A published report described the use of oral marimastat in four men with stage IV unresectable cholangiocarcinoma, meaning the cancer could not be removed by surgery.
- Healthy volunteers — a Phase 1 pharmacokinetic study was conducted in healthy adults to understand how the drug behaves in the body.
How is marimastat given?
In the published report on cholangiocarcinoma, marimastat was given orally at a dose of 10 mg twice daily. The Phase 1 trial registered in the EU CTIS studied a related product, PKL-021, administered orally at a dose of 400 mg. This indicates that oral administration is the route studied for this class of substance.
What do the clinical trials show?
One clinical trial is registered for this substance area in the EU CTIS. The trial was a Phase 1 study that enrolled 12 healthy adult subjects and is now completed. The primary objectives were to determine the pharmacokinetic profile — how the drug is absorbed, distributed, metabolised, and eliminated — after single and multiple oral doses. The study also evaluated the effect of food on the pharmacokinetic profile of a single dose.
The trial included a comparison product, Heparin Léčiva, given intravenously, as part of the study design. The registered product under investigation was PKL-021, a related oral formulation, rather than marimastat itself. The study was conducted in healthy subjects, meaning it did not evaluate effectiveness in any disease.
In addition to the registry trial, a published case series reported the use of oral marimastat in four men with stage IV unresectable cholangiocarcinoma. Tumour marker levels, measured monthly using CA 19-9, dropped sharply and remained low in two patients who appeared to respond. The mean survival in this small group was 21.5 months, with a range from 4 to 48 months. Side effects were reported as well tolerated.
What side effects are known?
In the published report on cholangiocarcinoma, side effects of oral marimastat were described as well tolerated. The report did not provide a detailed list of specific adverse events. No side effect information is available from the Phase 1 registry record for PKL-021.