The long road to FDA approval for Vasovist, the MR blood pool contrast agent, may be coming to an end. The FDA has begun its review of a response by the developer of the agent, formerly known as MS-325, to the agency’s approvable letter issued last January.
The long road to FDA approval for Vasovist, the MR blood pool contrast agent, may be coming to an end. The FDA has begun its review of a response by the developer of the agent, formerly known as MS-325, to the agency's approvable letter issued last January.
"The first action letter received in January was approvable, but we needed to answer certain questions the FDA posed. We believe we addressed those questions in our May response letter," said Mike Webb, chief executive officer of Epix.
This letter was submitted in May and accepted for review by the agency in July. The FDA now has six months to provide the Cambridge, MA-based company with an action letter. But any enthusiasm for a positive outcome by Epix is tempered by the fact that the government can change course at any moment.
Safety does not appear to be an issue. The FDA instead has focused on two aspects of with efficacy. One is the lack of a standardized protocol involved in obtaining the noncontrast, or time-of-flight, MR angiography scans. The second is the statistical handling of diagnostically uninterpretable images. Again, this relates to the noncontrast-enhanced imaging methods. The FDA questioned whether the high rate of uninterpretable time-of-flight scans might have artificially exaggerated the benefit of Vasovist.
While Webb won't say how Epix specifically addressed those concerns, he said the intent was to show that the noncontrast MRA scans were performed per their protocol, which required the use of the noncontrast MRA method in use at each hospital at the time of the trial.
Hospitals tend to have slightly different methods of performing noncontrast MRA and each one conforms quite closely to manufacturers' guidelines, which are FDA-approved, Webb said. But the FDA was not happy with the different methods, even though it had given the green light to the trial protocol at its inception, according to Webb.
"The FDA reserves the right to relook at things at any point in the process, even as late as an NDA submission. And that is what they've done," he said.
As the clinical sponsor, Epix didn't want to dictate a newer noncontrast MRA method for sites that had standardized their methods, he said. Company executives still believe this is a strength of the trial.
In their action letter of January, the FDA suggested that new studies, clinical or otherwise, might be the best way to address these issues. For now, Epix is not going that route. The company will be working with the FDA in the coming months to determine its next course of action, Webb said.
A problem for Epix - or any contrast agent manufacturer - is that FDA rules require manufacturers to compare their product to methods that do not involve contrast, according to Webb. The results from noncontrast-enhanced MRA, however, are generally viewed as inferior to those from contrast-enhanced MRA. The FDA's intent is for the manufacturer of the drug or contrast agent to prove that adding the contrast agent to the patient improves the imaging of the device alone, which is the noncontrast method, he said.
"That is the whole crux of the argument. You have no choice," Webb said. "It's just particularly frustrating for developers of the equipment and drugs, which takes up to 10 years, if the rules of the game are changing during that process."
Blood pool agents fit into either of two categories. One is macromolecular contrast agents, which are large molecules that clear from the bloodstream relatively slowly. These include gadomer-17 and P792. The alternative category is protein-binding agents such as Vasovist and B22956. None of Vasovist's competition has entered into phase III trials.
If Vasovist is approved for sale in the U.S., it would compete against MR contrast agents initially developed for the central nervous system. It could be approved as early as next year if the FDA accepts the Epix argument presented in its response and approves the drug later this year. Epix's partner for sales and marketing, Berlex, which is the U.S. subsidiary of Germany-based Schering, will handle marketing in the U.S.
Other parts of the world may have access before then. Webb said he expects Vasovist to be approved in Europe later this year and elsewhere in 2006.