Vasovist® (gadofosveset trisodium) is an injectable intravascular contrast agent discovered internally at EPIX and is designed to provide improved imaging of the vascular system using magnetic resonance angiography (MRA). EPIX's initial target indication for Vasovist is for use in MRA imaging of peripheral vascular disease, providing a breakthrough in the physician's ability to visualize the human vascular system and improve disease diagnosis and treatment.
Vasovist reversibly binds to the human blood protein albumin, allowing imaging of the blood vessels for approximately an hour after administration. With a single injection, Vasovist enables clear three-dimensional images of arteries and veins throughout the body. Vasovist may make it possible for physicians to detect vascular disease earlier and less invasively than with X-ray angiography, and provide an improved evaluation of potential therapeutic options including percutaneous intervention and vascular surgery.
In January 2008, EPIX reached agreement with the FDA on protocol and initiated a re-read of the Vasovist Phase 3 images. The positive results from the blinded, independent reread of Vasovist images were announced in April 2008. In the re-read of images, EPIX met all pre-specified endpoints prospectively agreed to with the FDA and EPIX plans to resubmit a New Drug Application (NDA) to the FDA for Vasovist in mid-2008.
Vasovist has been approved for marketing in 33 countries, including, among others, all 27 member states of the European Union, Switzerland, Turkey, Australia and Canada. The initially approved indication for Vasovist in the EU, Canada and Australia is the use in MRA imaging of the abdominal and limb vessels. The Turkish and Swiss authorities granted a whole body MRA indication.
Development History
In October 2005, the European Medicines Agency granted marketing approval of Vasovist for the 25 member states of the E.U. and Bayer Schering Pharma, EPIX's former partner for Vasovist, began marketing Vasovist in Europe in the second quarter of 2006. With the addition of Bulgaria and Romania to the E.U. in 2007, Vasovist is now approved in all 27 member states. In August 2006, the Australian Drug Evaluation Committee (ADEC) recommended to the Therapeutic Goods Administration (TGA) that Vasovist be registered for sale in Australia. Vasovist was approved for use in Switzerland in February 2006, Australia in September 2006, Canada in November 2006, and Turkey in 2007. Vasovist is currently marketed in Canada and 18 European countries, including, among others, Germany, the Netherlands, Italy, all Nordic countries, United Kingdom, and Switzerland.
In December 2003, EPIX Pharmaceuticals submitted a New Drug Application (NDA) to the FDA for the use of Vasovist in detection of vascular disease. In January 2005, EPIX received an approvable letter from the FDA for Vasovist pending additional clinical trials. In May 2005, EPIX submitted a response to the FDA, which was accepted as a complete response the following month. EPIX received a second approvable letter from the FDA in November 2005. The Company met with the FDA twice in early 2006 to discuss the path forward for Vasovist in the U.S.
In August 2006, EPIX received a letter from the U.S. Food and Drug Administration (FDA) denying the formal appeal to approve its novel blood-pool imaging agent Vasovist and turning down EPIX's request for an Advisory Committee to review Vasovist. In its response letter, the Office of New Drugs (OND) of the FDA also suggested that if EPIX decides to conduct additional clinical research to support approval, then rather than relying on a blinded re-read of previously submitted data and data from a new clinical trial, a safer course of action would be to conduct two new clinical trials to support the application for approval. EPIX submitted the appeal to the OND on June 30, 2006 in response to two prior approvable letters for Vasovist.
In June 2007, EPIX announced that it received a response from the FDA regarding the company's appeal for immediate approval of Vasovist. The response from the FDA is a result of a formal appeal EPIX filed on February 28, 2007 to the director of the Center for Drug Evaluation and Research (CDER) at the FDA, asking the CDER director to approve Vasovist. In the response, the FDA, while denying the immediate approval of Vasovist, indicated that further clinical trials may not be necessary to gain approval. The FDA had previously indicated that one or two additional pivotal clinical trials would be required for approval. In its response, the FDA stated that a blinded re-read of the images obtained from the previously completed Phase 3 clinical trials of Vasovist could support approval of Vasovist if the results are positive.
The NDA submitted for Vasovist was the culmination of an eight-year development program that included 18 clinical trials, 1,438 patients, and more than one million safety data points. In each pivotal trial, Vasovist met its primary endpoints. All four Phase 3 clinical trials demonstrated that Vasovist-enhanced MRA provided overall accuracy similar to X-ray angiography. In addition, it provides several important patient benefits:
- No arterial catheterization; only a single intravenous injection is needed
- No patient exposure to ionizing radiation
- No nephrotoxic dyes
- Complete vascular exam of multiple body regions for a more comprehensive diagnosis
- Less invasive than X-ray angiography, reducing patient discomfort and recuperation time
- Visualization of vessel wall structures (this is not part of the indication - it could be part of a follow-on indication however)
