Washington Editor

The FDA hurt EPIX Pharmaceuticals Inc. again, with news of another regulatory setback for Vasovist (gadofosveset trisodium) knocking 12.9 percent off the company's stock value Monday.

The shares (NASDAQ:EPIXD) traded down 93 cents to close at $6.28 as a result of the latest in a string of rejections for the blood-pool imaging agent, which already is approved in Europe. In the most recent denial, the FDA turned back a formal appeal from EPIX to approve Vasovist (formerly MS-325), as well as a request for an advisory committee review.

The company, of Lexington, Mass., appealed two prior approvable letters for Vasovist on June 30. Following the latest refusal, EPIX President Andrew Uprichard expressed frustration and disappointment.

"These are the same issues that were raised in the two approvable letters," he told BioWorld Today, "and they're issues that we believe we fully addressed, first in our complete response in May 2005 and more recently in our appeal. There's really nothing new in this response that we got."

Uprichard said that the company already has provided more information relating to the comparator scans used in past clinical trials - non-contrast magnetic resonance angiography (MRA) that the FDA recommended for comparative use prior to the studies - and the statistical treatment of uninterpretable images. That's what the agency wanted in those previous two approvable letters, in addition to requests for more clinical work through another study. (See BioWorld Today, Jan. 18, 2005, and Nov. 28, 2005.)

EPIX has yet to conduct any additional human tests, though, and now the FDA has upped that ante. In its most recent letter, its Office of New Drugs suggested that the company would be safer to conduct two new clinical trials to support approval rather than relying on a blinded re-read of previously submitted findings and data from a new study.

Uprichard noted that past studies that have included more than 1,400 patients in 18 trials indicated "that the data speak for themselves."

EPIX could further appeal the review, sending the matter up the chain at the FDA to the director of the Center for Drug Evaluation and Research. Should the company petition to overrule the Office of New Drugs, the subsequent review would take at least 30 days after the appeal is filed, although that could last longer.

"We obviously need time to go over our options," Uprichard said, "but I think it behooves everybody that we reach a decision on where we're going as soon as possible."

He said investors would be apprised quickly of the company's path forward.

The original new drug application included data from four Phase III studies demonstrating Vasovist's significant improvement in diagnostic efficacy compared to non-contrast MRA, and the overall accuracy of Vasovist-enhanced MRA was similar to the individual X-ray reader's inter-reader accuracy. Uprichard, who called non-contrast MRA "obsolete" because of current clinical practice that employs off-label gadolinium as a contrast agent, noted that Vasovist would enter a $100 million market with FDA approval. EPIX remains committed to bringing the product to the U.S. market, where it has targeted imaging non-coronary vascular disease as an initial indication.

An injectable intravascular contrast agent, Vasovist is partnered with Schering AG. That Berlin-based company has launched it in seven European Union countries, with more to come. It also is approved in Switzerland and was recently recommended for approval in Australia. Those clearances were based on the same data that the FDA has received.

Uprichard said EPIX expects to earn royalties on the lower end of a $200,000 to $800,000 range from those overseas sales this year. In the U.S., the partners would split profits evenly, as well as any additional development costs.

EPIX, which recently merged with Predix Pharmaceuticals Holdings Inc., features five clinical drug candidates in its pipeline behind Vasovist. (See BioWorld Today, April 4, 2006.)

The portfolio includes PRX-00023 in Phase III for generalized anxiety disorder, PRX-08066 in Phase II for pulmonary hypertension associated with chronic obstructive pulmonary disease, and PRX-03140 in Phase I for Alzheimer's. EPIX also has collaborations with Amgen Inc., of Thousand Oaks, Calif., and Cystic Fibrosis Foundation Therapeutics Inc., the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation in Bethesda, Md.