The FDA issued an approvable letter for EPIX Pharmaceuticals Inc.'s imaging agent MS-325, but it has required additional clinical studies before it will grant marketing clearance.
The news dropped the company's stock (NASDAQ:EPIX) $3.98 Friday, or 27.2 percent, to close at $10.67.
"We did not expect to be asked to perform additional clinical studies," said Michael Webb, CEO of Cambridge, Mass.-based EPIX. "We are very disappointed at that request. Nonetheless, we are happy that the product is approvable and that there were no deficiencies in the NDA with regard to safety and manufacturing."
The FDA's letter raised questions concerning the non-contrast magnetic resonance angiography (MRA) comparator scans used in the company's Phase III trials and the statistical treatment of uninterpretable images. MS-325 is the first in a new class of MRI blood pool contrast agents that is specifically designed for MRA.
EPIX will talk with the FDA to determine the next steps required for final approval. Webb declined to quantify the delay, saying he was not even sure whether a meeting with the FDA would occur in person or over the phone, and when it might take place.
"Right now, we're acknowledging the FDA's request to do additional studies," he told BioWorld Today. "The scope and range of those studies is yet to be determined."
EPIX filed its new drug application with the FDA in December 2003. At that time, the company said it had spent more than $85 million in discovery and development efforts associated with MS-325. Following the regulatory filing, a Prescription Drug User Fee Act date was scheduled for mid-October, but the FDA extended the action date when it asked for additional analyses of the submitted data. (See BioWorld Today, Dec. 17, 2003, and Oct. 6, 2004.)
The regulatory filing was based on data from four Phase III trials and 782 patients. In all four trials, MS-325 provided significant improvement in diagnostic efficacy compared to non-contrast MRA, and the overall accuracy of MS-325-enhanced MRA was similar to the individual X-ray reader's inter-reader accuracy.
MS-325 is the first molecularly targeted MRI contrast agent designed specifically for vascular imaging, Webb said. MS-325 (gadofosveset trisodium) binds reversibly to human serum albumin, brightening the blood for a prolonged period, allowing doctors to collect data using MRI equipment to diagnose and characterize vascular disease.
"It's a major clinical advance," Webb said, "because with a single intravenous injection, it lights up the vascular system in an MRI scanner very brightly and for over an hour. There is no other product on the market approved for vascular imaging with an MRI scanner in the U.S., so it would be a first.
"The macro-opportunity for the market is that MS-325 could have the potential to replace X-ray angiography and other invasive vascular imaging technologies."
Berlin-based Schering AG partnered with EPIX in June 2000 in a 50-50 worldwide sales and marketing agreement for MS-325. Schering filed an application for marketing approval in the European Union last year.
"Schering is forecasting that the product will be approved in Europe in late 2005," Webb said.
Founded in 1992, EPIX has two products in clinical trials, both invented in its laboratories, at which it uses its proprietary Target Visualization technology to create imaging agents. If MS-325 gets marketing clearance, it would be the company's first FDA-approved product. The company's second product, EP-2104R, has completed Phase I trials and will enter a Phase II program in the first half of this year. It also is partnered with Schering and is designed for the imaging of blood clots using MRI.