MBI's Albunex ends long FDA review with first U.S. ultrasound contrast approval

August 31, 1994

Mallinckrodt to sell pioneering echo contrast agent After nearlyfour years of premarket approval (PMA) review, the Food and DrugAdministration this month certified the first ultrasound contrastagent for sale in the U.S. Echocardiography agent

Mallinckrodt to sell pioneering echo contrast agent

After nearlyfour years of premarket approval (PMA) review, the Food and DrugAdministration this month certified the first ultrasound contrastagent for sale in the U.S. Echocardiography agent Albunex, developedand manufactured by Molecular Biosystems (MBI) of San Diego, willbe sold exclusively in North and South America by medical imagingcontrast supplier Mallinckrodt Medical of St. Louis.

The success of Albunex in penetrating the echocardiographymarket will be closely watched as an indicator of the future potentialof the ultrasound contrast market. The U.S. market potential ofAlbunex is fairly limited, however, relative to the universe ofultrasound exams performed in all applications. About 10 millionechocardiograms are performed annually in the U.S. Albunex mayreach 10% to 20% of that segment, according to Richard M. Stern,vice president of marketing for MBI.

The market for Albunex in the U.S. could amount to about $150million annually, estimated Daniel P. Moynihan, echocardiographymarketing manager for Mallinckrodt. The size of the ultrasoundcontrast market will grow dramatically as new agents come on-line.

"The whole ultrasound contrast market will be huge whennewer agents are developed, such as ones that will (image) myocardialperfusion," Moynihan said. "This agent is our firststep into the field of ultrasound contrast. We feel this willbe a growing and important field since it will bring additionalinformation to physicians at a lower cost (than other imagingmodalities)."

Eventually, contrast echocardiography could help reduce thenumber of more expensive medical procedures required, such ascardiac catheterization or angioplasty, he said.

Albunex consists of air-filled albumin microspheres, whichreflect ultrasound signals. The agent is indicated by the FDAfor use in enhancing opacification of the heart's left ventricle,Stern said. This function improves the cardiologist's abilityto resolve the endocardial border. It is necessary to see theborder when measuring wall thickness and determining regionalwall motion.

Mallinckrodt is responsible for developing general radiologyapplications for Albunex. The agent has shown potential in indicatingfallopian tube patency. Breast imaging could be another application,Moynihan said.

Sales of Albunex will start gradually, he said, as cardiologistslearn about not only a new type of contrast medium but an entirelynew procedure -- contrast echocardiography.

Mallinckrodt plans a targeted launch of the product, placingit first with a select group of physicians and hospitals. Thecompany expects that this introduction will help educate echocardiographyusers, including physicians and sonographers, about the new technique,and will better determine the agent's efficacy and ease of use,he said.

The commercial launch of Albunex in the U.S. could be hamperedby a lack of reimbursement for contrast echocardiography. Proceduraldata must be gathered and presented to the American Medical Associationto facilitate creation of a current procedural terminology (CPT)code for contrast echocardiography. CPT codes are required forboth Medicare and private insurance reimbursement of a medicalprocedure, Stern said.

Insurance payments for Albunex may be attained using relatedCPT supply codes for echocardiography, such as the code specifyingintravenous administration for stress echo studies, he said. Somedirect billing of users for the contrast agent is also expected.Mallinckrodt is formulating a reimbursement strategy for Albunexin the U.S.

While a price has not yet been determined for Albunex in theU.S., it is likely that the ratio of contrast to ultrasound examcost will be more favorable in this market than in Japan, wherethe agent has been selling since January for $75 per 5-mL vial,Stern said. Two to three vials are used for a single procedure.

"We feel that, in the U.S., the price of contrast mediawill not be as high as the cost of the procedure, assuming $100to $150 for contrast, which is comparable to Japan," he toldSCAN. "There is a big difference between the cost of an ultrasoundprocedure in Japan and the cost in the United States. An echoin Japan is about $100. An echo in the U.S. is in the $300 to$500 range."

Slow growth in Japan. Albunex was approved for market in Japanlast year (SCAN 10/6/93). MBI's Japanese licensee, Shionogi &Co., did not initiate sales until a National Health Insuranceprice was established by the Chuikyo, Japan's Central Social InsuranceMedical Council.

Japanese sales of Albunex have been growing steadily but ata slower pace than anticipated, Stern said. Part of the reasonmay be the agent's high price relative to the cost of ultrasoundimaging in that market.

Hafslund Nycomed, MBI's licensee for Albunex in Europe, hasnot yet initiated sales in that region, although national approvalwas received in two markets: Sweden last year and the U.K. shortlyfollowing the FDA announcement. Nycomed's strategy is to get approvalin the larger markets of Germany, France and Italy before launchof the product, he said.

The Norwegian contrast supplier, which purchased Sterling Winthrop'smedical imaging business last June (SCAN 7/13/94), will use itsU.K. approval to approach the European Union with a multistatesubmission for Albunex, Stern said.

Reflecting the close-knit nature of the world contrast mediamarket, MBI's other European licensee -- for its not-yet-approvedgastrointestinal ultrasound agent Oralex -- is Bracco of Italy.Bracco purchased Squibb Diagnostics last month. The Italian firmhas indicated a desire to withdraw from the Oralex licensing agreement,however, and the two partners are negotiating the matter,he said.Bracco picked up SonoRx, another GI ultrasound agent under development,with the Squibb deal (SCAN 8/10/94).

Albunex is the first approved transpulmonary agent able toimage the left ventricle, which cardiologists prefer to the rightventricle, he said. The left side of the heart pumps blood tothe body and is the location of most cardiac problems.

Schering's Echovist ultrasound cardiac agent, which is approvedin some markets worldwide, is a right-heart agent. This factormay have limited demand for the product, Stern said. The Germancompany has a second left-heart agent under development calledLevovist, which is farther back in the R&D pipeline. BothSchering agents are based on sugar molecules. Levovist uses astabilizer to achieve transpulmonary passage.

While clinical investigation has shown that Albunex can imageblood flow, MBI is not making this claim. The company has a secondcardiac ultrasound agent, FS069, under development, which willimage myocardial perfusion, Stern said. The company has not yetrevealed the nature of this agent.

"Certainly, the goal of contrast echocardiography is tohave an agent that flows through the myocardial tissue, representingan indicator of myocardial viability," he said.

Results of animal testing of FS069 showed it was able to viewmyocardial perfusion in almost 100% of the experiments, Sternsaid. The agent also has potential to visualize kidney, liverand testicular perfusion. MBI is preparing to file with the FDAfor approval to begin clinical trials with that agent.

It is hoped that by the time Albunex's competitors make itthough the FDA, MBI will be ready for market with its next- generationtechnology, he said.