Market for GI MRI contrast agents may get crowded as approvals near

New agents must overcome price issues

The first in a wave of gastrointestinal MRI contrast agents willsoon be attempting to establish a beachhead in medical imaging.In early December, the Food and Drug Administration granted AdvancedMagnetics of Cambridge, MA, approval to market Gastromark. Thedecision came just weeks after the regulatory agency sent an actionletter to Seattle-based Oncomembrane, stating that its GI agent,called Ferriseltz, was approvable. More such agents are on theway.

In addition, the FDA may act soon on a new drug application forGadolite, filed in September 1995 by Pharmacyclics of Sunnyvale,CA. The agency last month issued an approvable letter for theproduct, which will be marketed under license in the U.S. by E-Z-EMof Westbury, NY.

Next in line for the FDA's nod is Bracco of Milan, Italy. Thecompany filed an NDA in December 1995 for LumenHance, which wasdeveloped by ImaRx of Tucson, AZ. Meanwhile, ImaRx is developinga next-generation GI agent, called TomoRx, which promises to haveapplications in both MR and CT.

European physicians already have access to GI agents for MRI applications.Advanced Magnetics has been providing Gastromark for sale in Europe,where it is sold by the French pharmaceutical giant Guerbet underthe trade name Lumirem. Nycomed of Oslo, Norway, has also beenselling the GI agent Abdoscan on that continent. The Norwegiancompany has not yet announced plans to bring the agent to theU.S.

Each of these agents is designed to allow imaging of the bowelso as to distinguish the GI tract from adjacent abdominal structuresand from areas of suspected pathology. Despite the seeming utilityof MRI GI contrast, the technology does not have a successfulpast. Several years ago, physicians in the U.S. had commercialaccess to San Diego-based Alliance Pharmaceutical's Imagent GIproduct. The company began selling Imagent GI in 1993, but withdrewthe product from the market in 1994, citing poor sales (SCAN 9/28/94).Analysts believe the high cost of the agent—several hundreddollars per dose—and unpleasant side-effects were two reasonsfor poor acceptance of the product.

Are the new GI agents approaching the market headed for a similarfate? At the very least, the new products will not have to overcomeprice barriers in the U.S. Jerome Goldstein, president and CEOof Advanced Magnetics, expects Gastromark to be priced at about$25 per 300 mL. Either 600 or 900 mL will likely be administered,bringing the total cost to between $50 and $75 per patient.

Maintaining a low per-patient cost is believed to be essentialto the success of these agents, because the GI imaging marketis dominated by low-cost barium sulfate products used in x-rayimaging. Pharmacyclics executives have indicated that they believetheir agent, Gadolite, could be priced at $50 or less per dose.ImaRx executives concur, noting that their next-generation GIagent, TomoRx, would likely be in the same price range.

When Gastromark becomes available, probably within six months,the agent will be marketed in the U.S. by Mallinckrodt Medical,which has licensed the product for sale in the U.S., Canada, andMexico. Advanced Magnetics retains the right to co-market theagent in these countries but will exercise that right only ifsales by Mallinckrodt falter.

"I don't want to confuse their marketing and launch activitieswith our own," Goldstein said. "If we are unhappy withtheir performance, then we'll see what we can do."

Advanced Magnetics will receive a milestone payment of $500,000from St. Louis-based Mallinckrodt, as the result of having achievedFDA approval for the agent.

Gastromark will likely have the U.S. market for MRI gastrointestinalimaging to itself for much of this year. Oncomembrane, the developerof Ferriseltz, is in discussions with FDA reviewers to work outthe labeling that will be used with that product, according toTosh Tanaka, president of Oncomembrane. The labeling process forGastromark consumed about half a year.

"We are now responding to requests for additional documentationand then we are expecting final approval early this year,"Tanaka said. "This is a really big deal, because in the past,all the imaging agents were developed in the U.S. or Europe. Butour product is Japanese-made, Japanese-developed."

Otsuka Pharmaceutical, which owns Oncomembrane, develops, manufactures,and markets primarily pharmaceutical and nutritional products.The Japanese company has organized an international clinical studynetwork with research centers not only in Japan but also in theU.S., the U.K., Germany, and Spain, employing some 5400 staff.Headquarters in Japan delegates R&D authority to these officesto pursue research in basic areas.

Oncomembrane hopes to eventually develop the clinical supportto position Ferriseltz for use in dynamic studies of the bowel.

"Just seeing the tissue is not enough because intestinaldyskinesia is a motion problem," Tanaka said.

The company is in phase II clinical trials for this indication,using real-time MR imaging, and preliminary results were presentedat the Radiological Society of North America meeting last month.Meanwhile, the company is looking for a partner to sell Ferriseltzin the U.S., following final FDA approval.