By Steve Wagner Although Sonus Pharmaceuticals has officially withdrawn its new drug application (NDA) for the ultrasound contrast agent EchoGen, it has left the door open to eventually resume its quest for regulatory approval. Even so, development of
By Steve Wagner
Although Sonus Pharmaceuticals has officially withdrawn its new drug application (NDA) for the ultrasound contrast agent EchoGen, it has left the door open to eventually resume its quest for regulatory approval.
Even so, development of the product has ceased for the moment, and the company will refocus its business activities on its drug delivery technology and its blood substitute program.
"We wouldn't rule out further development of EchoGen," said Pamela Dull, a spokesperson for Sonus. "When that would beif at allI don't know."
Meanwhile, competing pharmaceutical companies are eyeing the potential market for their own ultrasound contrast agents with renewed enthusiasm in light of the Sonus withdrawal last month.
The decision to withdraw its NDA and discontinue clinical activity on the product, which has been approved for use in Europe, capped a tumultuous three-year period for Sonus. In 1997, the company joined a lawsuit against the FDA over the agency's regulation of ultrasound contrast agents. Although the suit was successfulwhich raised some eyebrows in the industrySonus may have won the battle but lost the war.
The following year, the FDA issued a nonapprovable letter for EchoGen, saying additional data were needed before approval could be granted. Sonus eventually received an approvable letter in April 1999.
The company's legal woes weren't over, however. Six months later, it settled a class-action lawsuit that claimed it did not communicate clearly about the status of the FDA's clearance of the product. Sonus and its patent licensing partner, Nycomed Amersham, also sued Molecular Biosystems and its marketing partner, Mallinckrodt, for patent infringement. A U.S. District Court eventually found that Molecular Biosystems and Mallinckrodt had infringed on two Sonus patents.
The EchoGen withdrawal has left competing pharmaceutical companies, including Alliance Pharmaceutical, closely watching the potential market for their own contrast agents.
"Our approval process with the FDA is going along smoothly, and we don't see any direct impact on us," said Gwen Rosenberg, vice president of corporate communications for Alliance. "It would be interesting if Sonus were willing to share the concerns that the FDA had. The assumption is that their problem is specific to their product, their manufacturing process, or something regarding usage."
Sonus president Michael Martino said that recent communications with the FDA led him to believe the agency had concerns about EchoGen specifically, as well as about the efficacy of all contrast agents designed to improve heart imaging through endocardial border delineation and left ventricular opacification.
Studies involving other agents have failed to show a correlation between improved endocardial border definition and the calculation of ejection fraction, an important measure of cardiac function, Martino said.
Also important were the agency's concerns that Sonus's activation procedure could create excessively large bubbles that might result in pulmonary embolism. Thus far, there has been no evidence of clinically significant embolism, Martino said.
To date, several new-generation ultrasound contrast agents are wending their way through the regulatory process, including Du Pont Merck's Definity (pjerflutren) and Nycomed Amersham's Sonazoid (NC100100). Molecular Biosystems/Mallinckrodt's Optison (octafluoropropane) has already been approved.
"What this does is make the market even more attractive for us, because one of the potential competitors is now gone," said Rosenberg, whose company has announced plans to purchase Molecular Biosystems. "It was certainly positive for us in that sense."
Speculation is that Alliance Pharmaceutical is dealing with the FDA in a more conciliatory fashion than did Sonus, whose relationship with the agency remained strained after it joined the 1997 lawsuit.
Alliance's Imavest is being developed jointly with Schering AG of Germany and received approvable status from the FDA in August. Final approval of the product could come during the first half of 2001, Rosenberg said.