Sonus wins regulatory breakthrough as FDA issues EchoGen approvable letter

Abbott and Sonus make plans for market launch

The light at the end of a long regulatory tunnel has finally appeared for Sonus Pharmaceuticals. The Bothell, WA, company on April 19 received an approvable letter from the Food and Drug Administration for EchoGen, Sonus’ ultrasound contrast agent. The news most likely means that Sonus will win full clearance for the product in less than six months.

The FDA’s letter covers the use of EchoGen in echocardiography applications, and states that Sonus must meet certain conditions before the agency will give the final nod of approval. The company was circumspect about the nature of the FDA’s requests, stating only that it was pleased by the letter and believes that it has an effective strategy for addressing the agency’s concerns and getting EchoGen cleared within a reasonable time frame.

Sonus’ reluctance to comment on the particulars of the letter highlights the difficulty the company has had throughout EchoGen’s regulatory process. Sonus first filed a new drug application for the agent in 1996, but ran into delays a year later when the NDA was suspended due to a lawsuit that Sonus and several other contrast firms filed against the FDA. The goal of the suit was to force the agency to explain why Molecular Biosystems’ agent, Optison, was being reviewed as a device rather than a drug (SCAN 4/30/97). The suit was successful in changing the way the FDA handled Optison’s review, and the agent was transferred to the FDA’s drug evaluation unit (SCAN 1/14/98).

Sonus’ victory was short-lived, however. Optison was cleared in December 1997, with EchoGen apparently hot on its heels. But the FDA dropped a regulatory bomb on Sonus in February 1998, when it handed the company a not-approvable letter for EchoGen. Many industry observers speculated that the not-approvable letter could be the FDA’s way of paying back the company for the lawsuit. Sonus executives, however, have stated that they have maintained good relations with the agency throughout EchoGen’s review.

The FDA’s not-approvable letter was based on several concerns the agency had regarding EchoGen’s application, including the interpretation of clinical images and the agent’s manufacturing process (SCAN 4/15/98). Although Sonus addressed the FDA’s concerns and submitted an amendment, its competitive edge with MBI seemed to be dulled as the San Diego company and its marketing partner, Mallinckrodt of St. Louis, moved forward with Optison’s launch.

With the approvable letter finally in hand, Sonus can once again begin the product-launch preparations that were put on hold last year. Sonus could receive final approval within three to six months, thus clearing the way for marketing partner Abbott Laboratories of Abbott Park, IL, to begin its campaign, according to industry analyst Alex Zisson of Hambrecht & Quist in New York City.

“The letter is a great achievement for the company,” Zisson said. “It looks like the end of the road is in sight, and then they’ll be able to turn (the process) over to Abbott. Sonus hasn’t been very explicit on the remaining items left to clear up before the full approval. But typically, (items listed in approvable letters) can be cleared up in a three- to six-month period, so we think Abbott should be able to launch by the end of the year.”

How will Sonus compete against MBI and Mallinckrodt, especially since those firms have had more than a year of lead time with Optison? Zisson predicts that Abbott will emphasize EchoGen characteristics such as the fact that it can be stored at room temperature and does not incorporate any blood-derived product. But differences between the products aside, Optison hasn’t made much of a splash in the market, according to Zisson.

“Optison’s been on the market for more than a year now, and it hasn’t made great inroads,” he said. “So I don’t think Abbott (will be) running into an extremely well-entrenched competitor.”

Sonus estimates that the U.S. market for ultrasound contrast consists of about 2.5 million to 3.5 million scans per year. Sonus president and COO Michael Martino declined to comment on the cost per dose of EchoGen, saying only that Sonus would price EchoGen competitively. The company plans to launch aggressive physician-education programs, since physicians and sonographers need to feel comfortable with the diagnostic quality of an ultrasound contrast exam before the product will take hold.

“We believe that the clinical and economic arguments for the use of the product are compelling. We also believe that we are faced with changing 20 to 30 years of practice, helping echocardiologists understand how they can add more value to suboptimal, technically difficult, or nondiagnostic exams by taking it a step further with contrast, as opposed to referring to MR or angiography,” Martino said. “Our marketing plans are based on the premise that this is a missionary market, and that education and training programs need to be well thought out. This is not a simple advertising and promotion thing.”

Although EchoGen was approved in Europe last July, Sonus and Abbott have not yet launched the product there. The two firms are seeking price and reimbursement approvals in major European countries, as well as variances to the agent’s European licenses that will enable them to manufacture EchoGen in Europe according to the same processes used for EchoGen in the U.S.

As for other applications of EchoGen, Sonus does intend to pursue radiology, particularly liver and kidney indications, Martino said. But for now, EchoGen’s approval is top priority.

“Job number-one is getting EchoGen approved for its pending applications,” he said.

The company’s good fortune didn’t stop with the FDA. On March 31, Sonus announced that the U.S. Patent Office issued certificates of re-examination for two patents covering EchoGen. The PTO’s action means that the company’s patents have survived a challenge from MBI with their key coverage intact, according to Sonus chairman and CEO Dr. Steven Quay.