Sterling Winthrop made it three this month, as its Omniscan agent became the third MRI contrast product to receive U.S. Food and Drug Administration marketing approval. The nonionic gadolinium agent will be sold in this market by Sanofi Winthrop, a joint
Sterling Winthrop made it three this month, as its Omniscan agent became the third MRI contrast product to receive U.S. Food and Drug Administration marketing approval. The nonionic gadolinium agent will be sold in this market by Sanofi Winthrop, a joint venture of Sterling and Elf Sanofi of France. Sterling is owned by Kodak, the leading medical imaging film vendor.
The FDA's nod for Omniscan's use in imaging the central nervous system followed approval of Squibb's Prohance MRI agent by a month and a half (SCAN 12/2/92). Unfortunately for Sterling Winthrop, the Radiological Society of North America meeting in Chicago fell within that brief time period.
Omniscan is licensed to Sterling by Nycomed of Oslo. The agent was actually developed by Salutar, Nycomed's Sunnyvale, CA-based U.S. subsidiary. Nycomed sells Omniscan outside the U.S. Late last year, the imaging pharmaceutical vendor received its first European approval for Omniscan in Great Britain.
Schering had a four-year monopoly on the MRI contrast media market with its Magnevist MRI agent, following FDA approval in the spring of 1988 (SCAN 6/22/88). All three agents are gadolinium-based, although Prohance and Omniscan are nonionic, while Magnevist is not.
Whether there is a clinical advantage for nonionic agents in MRI procedures is hotly debated. The FDA has requested suppliers not to hype this characteristic. Without the ionic/nonionic differentiation, however, all three agents are basically equivalent. This raises the possibility that price competition will reduce costs to U.S. users.
The cost of MR contrast--or more specifically, the lack of sufficient reimbursement to support this cost--is an issue of concern among radiologists and other users worldwide, according to Willy Eidsaunet, director of MRI product management for Nycomed.
"We have seen a lot of dose splitting with Magnevist in many countries, which I think you can trace back to the reimbursement situation," Eidsaunet told SCAN.
Ironically, a nonionic agent has theoretical advantages that may become apparent when dosages larger than the standard 0.1 mmol/kg are given. The results of at least one study suggest that larger doses of contrast are more effective when screening for cerebral metastases. This has some doctors worried that they will be paying for multiple doses while receiving the same reimbursement.
Omniscan, however, was approved only for a single dose of 0.1 mmol/kg. Prohance, on the other hand, was approved by the FDA with guidelines that, in some cases, allow for a cumulative total dose of 0.3 mmol/kg. Magnevist is approved only for the 0.1-mmol/kg dose in the U.S., but is approved for up to 0.2 mmol/kg in Europe.
Sterling Winthrop is evaluating higher dosages but did not make this a part of its original FDA application, according to a Sterling spokesperson.
Initial signs are that users may reap the benefit of price competition--at least when they stick to single doses. Sanofi Winthrop will offer Omniscan at a 2% discount to the going market price, according to the company.
The low price is part of a general strategic decision by Sterling Winthrop to keep pharmaceutical costs down. The high cost of drugs is a hot topic in the current debate over general health-care costs. But Omniscan's price was also set with an eye to supporting the agent's competitive position, the company said.
SINCE THERE ARE FAR FEWER MRI SYSTEMS installed worldwide than x-ray and CT units, the market for MRI contrast is significantly smaller than radiographic contrast. But this will change, according to Eidsaunet.
"It is anybody's guess where we will end up, but I think that, by the turn of the century, the MR market might be approaching the size of the x-ray market today."
The current worldwide MRI contrast market is approaching $500 million annually, he said, while radiographic contrast sales are around $2 billion.
Sales of MRI contrast will also depend on the rate of conversion to contrast use in MRI procedures, he said. This varies widely among countries and applications.
The average MRI contrast usage rate worldwide is between 30% and 40%. In Europe, Germany and France have the highest rates of contrast use. Germany's usage is greater than that of the U.S., while France is at least on a par with this country, he said.
In terms of MRI applications, the highest use of contrast is in brain studies, while there is more variance in use for spinal imaging. Use outside the central nervous system is limited in large part because of a lack of regulatory approval.
Agents coming down the pipeline will be more organ-specific. Nycomed has completed phase II trials of a manganese MRI agent for use in the liver and pancreas, Eidsaunet said.
"There is uptake in normal tissue in these organs and minimal uptake in most tumors. Some kinds of tumors may have some uptake on the edge, which could potentially be useful for differentiation," he said.
As MRI contrast use increases, system vendors will be modifying their equipment to optimize the clinical benefits.
"One could perhaps get more benefit out of using contrast agents if the pulse sequences were tailored a little, since the agents have an effect on the relaxivity parameters in MR. If you could use slightly shorter TRs and TEs with contrast agents, that (greater speed) could be a beneficial effect."
Instrumentarium is one MRI company that has already tailored sequences for contrast use, Eidsaunet said. Instrumentarium and Nycomed are also working on a project to develop a low-field MRI technique called Overhauser MRI (OMRI). OMRI requires the use of a specialized contrast agent in conjunction with an ultralow-field MRI system (SCAN 2/13/91).
Clinical studies in Europe have found advantages in MRI breast imaging when specific pulse sequences are combined with contrast agent use, he said. Results have shown high potential to differentiate malignant from benign tumor by the difference in their contrast uptake.