New MR contrast agent enhances liver tumors, GI tract

An experimental contrast medium designed specifically for MR imaging of the liver and GI tract has entered phase III studies.

The agent, called CMC 001, enhances primary liver cancer as well as liver metastases that commonly occur in cancer patients. The orally administered agent may be helpful in visualizing liver function by following the metabolism and excretion of manganese in the liver cells. It also enhances the bowel and biliary tract.

Two clinical studies conducted as part of phase I and II research - one in Copenhagen, the other in Nijmegen, the Netherlands - have documented "excellent" contrast enhancement and only minimal adverse effects, according to the developer of the agent, Swedish firm CMC Contrast. Phase III research began Sept. 27 at the Karolinska University Hospital in Huddinge, Sweden. The company expects the trial to be completed and fully reported by the end of June 2006.

CMC Contrast strategists plan to address the European market first, seeking EU approval by the end of 2007 with market release six to 10 months after application. The next step would bring CMC 001 to the U.S., pending FDA approval. The company expects to apply for FDA approval by mid-2008. If the timeline unfolds as hoped, the agent will begin the Japanese regulatory process by the end of 2008.

CMC Contrast was founded in 2000 by Dr. Henrik S. Thomsen of the radiology department at Herlev University Hospital outside Copenhagen. Thomsen holds the patents on the liver imaging agent. Its development has been funded by venture capital companies Öresund Healthcare Capital and Malmöhus Invest.

CMC Contrast plans to work with one or more international pharmaceutical companies in launching the agent. Several firms have expressed an interest in marketing the product, according to Dr. Lars Vedin, general manager of CMC Contrast.

"We do not wish to rush these discussions, but based on experience, phase III is an important time for making commercial deals," Vedin said.

Any such agreements will, of course, depend on successful completion of these trials and approval by regulatory agencies. Company executives describe the contrast agent as being very safe.

"Very few adverse events have been reported with CMC 001, and those reported are mild," Vedin said. "This is because the manganese is delivered to the liver and the bile ducts through absorption in the GI tract and delivered via portal circulation."

CMC 001, composed of manganese and absorption promoters, is administered orally, absorbed by the small bowel, and transported to the liver, where manganese ions are picked up by hepatocytes. (CMC 001 also enhances the gastrointestinal tract, as enough manganese remains there to allow effective MR imaging.)

Only a limited quantity of manganese circulates systemically, according to Vedin. This reduces adverse effects of the chemical on cardiac rhythm and the central nervous system. The manganese absorbed in the liver is excreted through the biliary system and into the bowels, returning liver concentrations of the element to precontrast values within several days.