History of ABLAVAR®

History of ABLAVAR®

The first blood-pool contrast agent, ABLAVAR® (formerly known as MS-325, MS 32520, ZK 236018, gadofosveset, gadofosveset trisodium, AngioMARK, and Vasovist) was invented by Dr. Randall Lauffer, a chemist at Harvard's Massachusetts General Hospital.

Dr. Lauffer left his job in order to further develop his idea for the new blood-pool contrast agent, and as a result he founded Metacorp, Inc. based in Cambridge, Massachusetts, United States (U.S.). Later, the company was renamed EPIX Pharmaceuticals Inc.

EPIX initiated several pre clinical and clinical trials spanning the years 1988 to 2009 to assess the safety and clinical utility of the new blood-pool contrast agent they called MS-325 (former code name of gadofosveset trisodium) for the detection of peripheral vascular disease (PVD) and coronary artery disease. Additional trials were conducted to evaluate gadofosveset as an aid in diagnosing breast cancer.

A Phase I safety trial of MS-325 was completed during the first quarter of 1997. The first Phase II trial was initiated at multiple clinical sites to test the safety and preliminary efficacy of MS-325 for the evaluation of PVD.

Epix joined forces with Siemens Medical Systems Inc. and Mallinckrodt (Tyco International) aimed at combining gadofosveset trisodium (marketed by Mallinckrodt as AngioMARK®) enhanced MRI with advanced imaging and 3D computerized visualization technologies. Phase III trials of gadofosveset for the detection of aortoiliac occlusive disease (AIOD) in patients with PVD or abdominal aortic aneurysm were initiated.

Schering AG acquired worldwide exclusive rights (except for Japan and the U.S.) from EPIX to develop and market gadofosveset under the trade name Vasovist. Under the terms of this agreement, EPIX was responsible for the completion of clinical trials and filing for approval in the U.S., while Schering AG took responsibility for the clinical investigation of gadofosveset outside the U.S. Mallinckrodt was responsible for long-term supply for gadofosveset for clinical development and sales. Schering's subsidiary Berlex marketed the product in the U.S. after the approval.

EPIX reacquired the Japanese rights for gadofosveset from Daiichi Radioisotope Laboratories and exclusively licensed them to Schering AG. With this agreement, Schering AG gained worldwide rights for gadofosveset, with the sole exception of the U.S.

In December Epix submitted a new drug application (NDA) to the U.S. FDA regarding gadofosveset trisodium (Vasovist) for vascular imaging using magnetic resonance angiography (MRA). The NDA was based on the results of 18 clinical trials in 1438 patients who received gadofosveset trisodium.

In February the NDA for gadofosveset trisodium was accepted for filing by the FDA to proceed through a standard review cycle.

In June EPIX submitted a NDA for approval of gadofosveset trisodium (Vasovist) for MRA in the European Union (EU).

The FDA issued an approvable letter for gadofosveset trisodium in January, indicating that at least one additional clinical trial, and a re-read of images obtained in previously completed Phase III trials would be necessary before approval. However, no safety or manufacturing issues were raised in the approvable letter.

In October gadofosveset trisodium was approved by the European Commission in all 25 member states of the EU for MRA the indications of peripheral arterial occlusive disease, aortoiliac occlusive disease, critical limb ischemia and renal artery stenosis. It was then marketed in Europe under the trade name of Vasovist® by Bayer Schering Pharma for use in MRA in adults with suspected or known vascular disease of the abdomen and/or extremities. In Switzerland (non-EU), gadofosveset trisodium was approved for contrast-enhanced MRA in patients with suspected or known vascular disease, including imaging of the intra- and extra cerebral vessels, as well as pulmonary embolism (PE) and deep vein thrombosis (DVT).

Gadofosveset trisodium (Vasovist®) was approved in Canada in November for use as a MRA contrast agent for the visualization of abdominal or limb vessels in patients with known or suspected vascular disease. The approval was based on data from four multicenter, phase III clinical trials showing that the overall accuracy of gadofosveset-enhanced MRA was similar to that of catheter-based X-ray angiography. This was the 30th country in which the agent was approved for marketing.

In late June EPIX filed an appeal with FDA regarding Vasovist® approvable letters and in July FDA extended the review of EPIX Pharmaceuticals’ appeal of Vasovist™.

In January EPIX reached an agreement with FDA on protocol and initiated a re-read of the gadofosveset trisodium Phase III data, and in July the NDA was resubmitted to FDA.

In December the FDA approved the use of gadofosveset trisodium (Vasovist®) for the evaluation of AIOD in adults with known or suspected PVD, making it the first MRA contrast agent approved in the U.S.

BayerSchering Pharma discontinued marketing of Vasovist®.

In April Epix sold the U.S. (including Puerto Rico), Canadian, and Australian rights for gadofosveset trisodium (formerly marketed by BayerSchering Pharma as Vasovist®) to Lantheus Medical Imaging, Inc., who renamed the agent ABLAVAR®. EPIX, however, continued to own European and other non-U.S. rights for the blood-pool contrast agent.

In March EPIX acquired global marketing rights for gadofosveset trisodium outside the U.S., Canada, and Australia from Bayer Schering Pharma.

In July 2009 Epix declared bankruptcy and all of the remaining assets of the company was later sold.

Lantheus Medical Imaging, Inc. launched ABLAVAR® in the U.S in January and acquired exclusive worldwide rights for gadofosveset trisodium in an action of the remaining assets from of Epix Pharmaceuticals in July. ABLAVAR® (gadofosveset trisodium) is today approved for marketing in the United States and in 37 countries outside the United States, including Canada, Australia, all 27 member states of the European Union, Norway, Iceland, Switzerland, Turkey, Korea, Bosnia-Herzegovina, Serbia, and Ukraine. Gadofosveset trisodium has been used in over 90,000 patients. Moreover, several late stage clinical trials are currently ongoing.
Created 08/09/2011 Last updated 19/03/2012