MS-325 (formerly marketed as Vasovist, gadofosveset trisodium, by Bayer Schering Pharma) 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).
On December 22, 2008, EPIX announced that the U.S. Food and Drug Administration (FDA) granted marketing approval of MS-325 under the trade name Vasovist for the evaluation of aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease. AIOD occurs when iliac arteries become narrowed or blocked and may prevent the sufficient transport of oxygen and/or blood throughout the body. In April 2009, EPIX announced that the company sold the U.S. (including Puerto Rico), Canadian and Australian rights for Vasovist to Lantheus Medical Imaging, Inc. EPIX will continue to own European and other non-U.S. rights for MS-325 enabling it to pursue further monetization of these rights. In addition to the United States, MS-325 is approved for marketing under the trade name Vasovist in all 27 member states of the European Union, Norway, Iceland, Switzerland, Canada, Turkey, Australia, Korea, Bosnia-Herzegovina, Serbia and Ukraine. The initially approved indication for MS-325 in the EU, Canada and Australia is for use in MRA imaging of the abdominal and limb vessels. The Turkish and Swiss authorities granted a whole body MRA indication.
MS-325 reversibly binds to the human blood protein albumin, allowing imaging of the blood vessels for approximately an hour after administration. With a single injection, the agent enables clear three-dimensional images of arteries and veins throughout the body. MS-325 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.
MS-325 under the trade name Vasovist is the first contrast agent approved for marketing in the United States for use with MRA, a non-invasive modality for imaging blood vessels. In 2007, there were approximately 1.3 million MRA procedures performed in the United States using contrast agents not specifically approved for this procedure. MRA is a less invasive procedure than x-ray angiography, allowing for reduced patient discomfort and recuperation time and unlike x-ray angiography, MRA does not expose patients to ionizing radiation. Vasovist has now been approved for marketing in 38 countries, including the United States, based on data from four multi-center, Phase 3 clinical trials that showed that the agent's overall accuracy was similar to that of catheter-based x-ray angiography, as determined by blinded readings.
Development History
United States
In December 2003, EPIX Pharmaceuticals submitted a New Drug Application (NDA) to the FDA for the use of MS-325 (formerly marketed as Vasovist®, gadofosveset trisodium, by Bayer Schering Pharma) in detection of vascular disease. In January 2005, EPIX received an approvable letter from the FDA for the agent 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 MS-325 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 MS-325 under the trade name Vasovist and turning down EPIX's request for an Advisory Committee to review the agent. 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 the agent.
In June 2007, EPIX announced that it received a response from the FDA regarding the company's appeal for immediate approval of MS-325 under the trade name 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 the agent. In the response, the FDA, while denying the immediate approval of the agent, 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 MS-325 under the trade name Vasovist could support approval of the agent if the results are positive.
The NDA submitted for MS-325 under the trade name 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, the agent met its primary endpoints. All four Phase 3 clinical trials demonstrated that MS-325-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)
In January 2008, EPIX reached agreement with the FDA on protocol and initiated a re-read of the MS-325 Phase 3 images. The positive results from the blinded, independent reread of the 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 submitted a New Drug Application (NDA) to the FDA for MS-325 under the trade name Vasovist on June 30, 2008. EPIX announced FDA marketing approval of MS-325 under the trade name Vasovist to evaluate aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease on December 22, 2008.
Global
In October 2005, the European Medicines Agency granted marketing approval of MS-325 for the 25 member states of the E.U. and Bayer Schering Pharma, EPIX's former partner for MS-325, began marketing the agent in Europe in the second quarter of 2006. With the addition of Bulgaria and Romania to the E.U. in 2007, MS-325 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 the agent be registered for sale in Australia. MS-325 under the trade name Vasovist was approved for use in Switzerland in February 2006, Australia in September 2006, Canada in November 2006, and Turkey in 2007. In 2008, the agent was approved for marketing in South Korea, Bosnia-Herzegovina, Serbia and Ukraine. Including the United States, the agent has been approved for marketing in 38 countries.
