FDA approves first imaging agent for MR angiography in U.S.

After prolonged deliberation and repeated demands for more research, the FDA has approved Vasovist (gadofosveset trisodium), the first contrast imaging agent to gain regulatory clearance specifically for MR angiography.

The agency approved the New Drug Application for Vasovist on Dec. 24. Epix Pharmaceuticals, the agent's developer in Lexington, MA, welcomed the announcement.

"Vasovist is a first-in-class contrast agent with several unique characteristics that we believe will allow it to become a market leader in the U.S.," said Elkan Gamzu, Ph.D., interim chief executive officer of Epix, in a release.

Phase III clinical trials established the overall accuracy of Vasovist as similar to the diagnostic capabilities of catheter-based x-ray angiography. It is already in use in 34 countries outside the U.S. Its advantages include good resolution, high signal per dose, a long imaging window timeframe, and single-dose imaging of multiple vessel beds, according to Gamzu.

Gadolinium-based contrast media, such as Magnevist (gadopentetate dimeglumine) and Omniscan (gadodiamide), were employed on an off-label basis to enhance an estimated 1.3 million MRAs in 2007, according to Epix officials.

Vasovist, initially called MS-325, was widely hailed by radiologists for its diagnostic potential as MRI's first dedicated blood-pool agents when it was introduced in the early 1990s.

Epix officials expressed optimism about the possibility of FDA approval of the agent after phase III trials were completed in 2003. The FDA did not issue an approvable letter for Vasovist until January 2005, however. Final approval was then delayed nearly three more years as the company conducted additional research to answer questions about agent's efficacy and its investigators' research methods.

Following more research, Epix resubmitted its New Drug Application to the FDA on June 30, 2008.

As a blood-pool agent, Vasovist has inherent advantages over other MRI contrast media, said Dr. Martin Prince, a professor of radiology at Weill Medical College, Cornell University.

"Unlike extracellular contrast, Vasovist remains concentrated in the blood for more consistent imaging throughout the vasculature. The difference will be especially evident for venous imaging," he said in an interview.

Unlike other gadolinium agents that rapidly clear from the blood and have a narrow imaging window, Vasovist also contains albumin-binding properties. As such, it provides good resolution angiography, a high signal per dose, a long imaging window timeframe, and single-dose imaging of multiple vessel beds, Epix said.

"[Vasovist] will be great for checking patients for internal bleeding, detecting intramural bleeding associated with aortic stent-grafts, and identifying sites of gastrointestinal bleeding generally," Prince said.

Contrast-enhanced MRA may become an alternative to the labeled white blood cell imaging currently used for these applications, according to Prince.

When radiologists scan blood vessels using MRA without any contrast, they are unable to interpret the images between 10% and 30% of the time, the FDA said.

Because Vasovist is injected into a peripheral vein and no artery is punctured, the potential risks are fewer than using x-rays to detect blood vessel abnormalities, according to the FDA.

Epix Pharmaceuticals established Vasovist's safety and efficacy in two phase III clinical trials of patients with known or suspected aortoiliac disease. The FDA requested a blinded reread of the images obtained with Vasovist in 2008 to confirm the drug's efficacy from prior studies.

On the first endpoint regarding sensitivity, all three of the readers met the endpoints (p<0.001), according to the company. The second endpoint brought about the same conclusion, when Vasovist showed better specificity than noncontrast MRA. On the third endpoint, all three readers found Vasovist sensitivity and specificity to be significantly better than chance alone.

Epix plans to enter into a marketing and commercialization partnership or to sell the marketing rights to the product outright.

"Vasovist is a core part of our corporate strategy in that its monetization may further our ability to successfully and cost-effectively develop and build our valuable pipeline of product candidate assets," a company spokesperson said.

Bayer Schering Pharma holds global marketing rights to Vasovist until March 1, at which time rights transfer to Epix.