FDA clears MBI’s Optison agent for ultrasound cardiac applications

More litigation looms for Mallinckrodt and MBI, however

Ultrasound contrast agent developer Molecular Biosystems and its marketing partner Mallinckrodt have found another reason to celebrate the new year. The companies on Dec. 31 received news that the Food and Drug Administration has finally cleared Optison, a second-generation perfluorocarbon ultrasound contrast agent developed by MBI.

The news wasn't all good for the two companies, however. A lawsuit filed by the two firms to declare patents held by Sonus Pharmaceuticals to be invalid was dismissed by a U.S. District Court judge just days after Optison's clearance. Sonus also announced last week that it has filed a patent infringement lawsuit against MBI and Mallinckrodt.

The litigation news was overshadowed by Optison's approval, however. Optison joins MBI's first-generation Albunex agent as the only ultrasound contrast agents on the U.S. market. The product's approved indications are for use in patients with suboptimal echocardiograms to opacify the left ventricle and to improve the delineation of the left ventricular borders.

While Albunex and Optison have similar indications in cardiac imaging, Mallinckrodt will shift its marketing effort and emphasize Albunex's capabilities for assessing fallopian tube patency. Optison will be positioned as the company's ultrasound contrast agent for cardiac imaging, said Neal Muhilly, vice president of ultrasound for Mallinckrodt.

The two companies believe that the improved performance of Optison will lead to widespread market acceptance, an achievement that eluded Albunex due in part to its short blood persistence time. Optison lasts more than four minutes with a single injection, while Albunex typically persists between 30 and 45 seconds, said Bobba Venkatadri, president and CEO for San Diego-based MBI.

The short persistence time led to an efficacy level for Albunex of around 60% in converting nondiagnostic studies to diagnostic exams. In contrast, clinical studies have shown a 95% efficacy level for Optison, Venkatadri said.

"In today's healthcare environment, for somebody to spend $100 or $150, they have to have greater than 60% clinical utility," he said.

Optison also will have a lower dose than Albunex. The new agent will be packaged in boxes of four 3-mL vials, with a price per vial of $110. Albunex is sold in 10- and 20-mL vials with a price per vial of $75. The average dose of Albunex is 15 mL, Venkatadri said.

Sales of Optison have begun, and it has already been used clinically, according to Barbara Abbett, vice president of communications for St. Louis-based Mallinckrodt. The firm plans to tout Optison at the American College of Cardiology meeting in March, as well as the American Society of Echocardiography show in June, Abbett said.

Clinical trials for other applications of Optison are ongoing. Three phase II studies evaluating cardiac perfusion have been completed, and phase III studies are expected to begin in the first quarter. MBI estimates that 3.5 million nuclear medicine myocardial perfusion studies are performed each year, and the company believes that Optison-enhanced ultrasound could be competitive with those procedures.

In radiology applications, a third phase II study evaluating the agent in liver imaging is near completion, with phase III trials slated to begin by the first half of the year. Investigational work with kidney and transcranial imaging is also under way.

The FDA's decision to approve Optison brings to a close a regulatory journey that experienced considerable twists and turns. Approval for the agent, initially called FS069, appeared to be imminent nearly a year ago, when it received a recommendation for approval without conditions by the FDA's Radiology Device Advisory Panel on Feb. 24.

With clearance apparently at hand, Bracco Diagnostics, DuPont Merck Pharmaceutical and its partner ImaRx, and Sonus filed lawsuits asking the FDA to eliminate the disparity in the regulation of contrast agents. Unlike other contrast agents that have historically been regulated as drugs in the FDA's Center for Drug Evaluation and Review (CDER), FS069 and Albunex had been regulated as devices in the FDA's Center for Devices and Radiological Health (CDRH). In July, the FDA decided to review all ultrasound contrast agents as drugs (SCAN 8/6/97).

Although the regulatory review issue has been resolved, patent disputes between the companies continue to flare. Bothell, WA-based Sonus announced early this month that a lawsuit filed by MBI and Mallinckrodt seeking to invalidate Sonus ultrasound contrast patents has been dismissed by the U.S. District Court for the District of Columbia. In addition, Sonus announced that it has filed a patent infringement lawsuit in a U.S. District Court in Seattle, alleging that Optison infringes Sonus patents. A patent infringement suit filed last year against MBI, Mallinckrodt, and Sonus by Nycomed Amersham is pending (SCAN 9/17/97).

Although the legal tussles have cast a pall over the ultrasound contrast market, industry observers are hoping that the new agents will open up the market in a way that Albunex never did. Agents like Optison and EchoGen from Sonus should help ultrasound realize its potential as the low-cost modality of the future, according to Alex Zisson, managing director for healthcare research at Hambrecht & Quist in New York City.

"Anything that can improve ultrasound as a way to reduce the number of more expensive procedures is bound to draw interest," Zisson said.