Gadofosveset [MS 325, MS 32520, Vasovist, ZK 236018], a gadolinium-based chelate, is an injectable angiography imaging agent for use in magnetic resonance imaging (MRI) scans. The agent is being developed by EPIX Medical (formerly Metasyn) for diagnostic imaging of blood vessels of the cardiovascular system.Gadofosveset has potential as an alternative to the range of x-ray, invasive, catheter-based angiograms and thallium stress tests currently used in the diagnosis of coronary artery disease. The agent may also have applications in the diagnosis of peripheral vascular disease, thrombosis and breast cancer. Unlike conventional MRI contrast agents, gadofosveset binds to serum albumin in the blood and moves with the blood through the arteries and veins for an extended period of time before being excreted by the kidneys. The MRI with gadofosveset allows 3D images of the whole body to be accessed in one imaging session. Moreover, it makes it possible to view vessel structures.EPIX Medical has acquired an exclusive licence from the Massachusetts General Hospital to a certain technology, including patents and patent applications, that relates to the company's product candidates such as gadofosveset.EPIX Medical, Mallinckrodt (Tyco International) and Schering AG signed several agreements to develop, manufacture and market gadofosveset (formerly known as Mallinckrodt's AngioMARK®). Initially, in June 2000 Schering AG acquired worldwide exclusive rights (except for Japan) from EPIX Medical to develop and market gadofosveset. Under the terms of the agreement, EPIX Medical is responsible for the completion of clinical trials and filing for approval in the US, while Schering AG undertakes responsibility for clinical investigation of gadofosveset outside the US. Mallinckrodt is responsible and will undertake a long-term supply contract for gadofosveset for clinical development and sales. Schering's subsidiary Berlex will market the product in the US after the approval via its 100 sales representatives.In January 2001, EPIX Medical reacquired the Japanese rights for gadofosveset from Daiichi Radioisotope Laboratories and exclusively licensed them to Schering AG. With this agreement, Schering AG has worldwide rights for gadofosveset. The financial terms of the Japanese rights agreement included a US$3 million upfront fee, and additional milestone payments from Schering AG to EPIX Medical.On 16 December 2003, EPIX announced that it submitted an NDA to the US FDA for gadofosveset for vascular imaging using magnetic resonance angio-graphy (MRA). This is the first NDA filed for approval with the FDA for a MR contrast agent for the primary indication of MRA. The NDA is based on the results of 18 clinical trials in 1438 patients who received gadofosveset.[1]In February 2004, EPIX Medical announced that the NDA for gadofosveset was accepted for filing by the FDA and would proceed through a standard review cycle.[2]The approval for gadofosveset is expected at the end of 2004. In January 2004, Schering reported at the JP Morgan Healthcare Conference that it plans a product launch in the US sometime in 2005.EPIX and Schering have completed four phase III studies in patients with suspected atherosclerotic disease in the aortoilliac, pedal and renal arteries for inclusion in the NDA submission. These trials were conducted at 86 clinical sites and involved 782 patients. The blinded reading of almost 4000 vessels showed that gadofosveset improved diagnostic accuracy of MRA compared with non-contrast MRA. The diagnostic efficacy of gadofosveset-enhanced MRA was comparable to that of x-ray angiography.[3]These trials were initiated in accordance with the recommendations of the FDA to expand gadofosveset's target indication of aortoiliac occlusive disease to a broader peripheral vascular disease indication.[4]In July 2004, EPIX Medical initiated a multicentre, post-NDA trial with gadofosveset for use in high-resolution vessel imaging for the characterisation of vascular wall structures and vulnerable plaque. The trial will investigate whether gadofosveset has an extended imaging window above and beyond that which was demonstrated in phase III studies.[5]In June 2004, Schering submitted gadofosveset for approval in Europe for use as a conrast agent for MRA.[6]The launch in Europe is projected for 2006 (Schering, Annual Report 2003).Schering has initiated its first feasibility, multicentre (Europe, US), phase III clinical trial with gadofosveset for the imaging of coronary artery disease in approximately 50 patients. This trial follows a successful completion of phase II feasibility studies with gadofosveset in the imaging of coronary artery disease and breast tumour imaging.In July 2004, EPIX announced that it initiated a multicentre phase IIa feasibility clinical trial with gadofosveset in the imaging of both the coronary arteries and myocardial perfusion.[7]EPIX Medical is conducting preclinical investigation with gadofosveset for myocardial perfusion and rheumatoid arthritis.EPIX Medical, Mallinckrodt and Pfizer have announced a collaboration to investigate MRI imaging with gadofosveset in the diagnosis and monitoring of female sexual arousal dysfunction (FSAG). EPIX Medical completed enrolment in a phase II clinical feasibility trial using gadofosveset for this indication. It is estimated that more than 10 million women in the US suffer from FSAD.EPIX Medical was granted a US patent No. 6,676,929 covering composition-of-matter claims for the chemical structure of gadofosveset. The patent is entitled "Diagnostic Imaging Contrast Agents With Extended Blood Retention". Its expiry date is August 2015. However, under provision of the Hatch-Waxman Act, the terms of the patent may be extended following FDA approval.[8]In its 2002 Annual Report, Schering predicted that gadofosveset has the potential to reach peak sales of EUR100 million, 3 years after launch – at the time, launch in the US was anticipated in 2005.Earlier, at an analyst presentation in Berlin in March 2002, the company stated that launch in the US was planned for 2004.