FDA grants priority review to AVM’s lymph node agent

Contrast agent supplier Advanced Magnetics scored a coup this month when the Food and Drug Administration granted priority review to the company’s new drug application (NDA) for its MRI contrast agent for the diagnosis of lymph node cancer. Advanced Magnetics submitted its NDA for Combidex, the first such agent to be submitted for approval, in January (SCAN 1/12/00). When it announced the FDA’s decision Feb. 1, the company noted that priority reviews are required to be completed within six months, and that it expects a decision from the FDA on Combidex’s approval by June 19.

“We don’t know if there will be an advisory panel or not; that’s still up in the air,” said Jerome Goldstein, CEO of the Cambridge, MA, company. “But having an advisory panel will not change the action date. By statute, the FDA has until June 19 to give us an action letter.”

Much rides on this drug clinically and financially. The FDA conferred priority status because the agent was judged to have the potential to provide a significant improvement in the treatment or diagnosis of disease. Currently lymph node cancer is diagnosed using either CT or MRI, but neither is very effective. Both are riddled with false negatives and false positives, leading, in some cases, to unnecessary surgery. Clinical tests indicate that Combidex could vastly improve the performance of MRI and, potentially, reduce the number of surgeries.

Just as the agent could decisively affect patient management, it could also have a dramatic effect on the future of Advanced Magnetics. Throughout its 19-year history, the company has worked to develop a blockbuster imaging agent. Back-to-back approvals of the first liver imaging agent, Feridex I.V., in September 1996, and GI agent GastroMark in December 1996, raised expectations for revenues that Advanced Magnetics failed to meet. Combidex represents the best, and perhaps last, chance for the company to make good.

“You don’t have to be a rocket scientist to understand that we can’t lose money forever,” Goldstein said.

If approved by the FDA, Combidex will be the first commercial agent of its kind, and will fulfill an unmet need: In addition to reducing the number of false findings associated with lymph node cancer, Combidex can help physicians localize the affected nodes and thereby serve as a means for directing biopsy and surgery. With its NDA, the company is seeking this indication, as well as the use of Combidex in the staging of metastatic lymph node involvement for various cancers, including those of the breast and prostate.

How Combidex will get into the hands of physicians, however, is still uncertain. Small drug developers have frequently established marketing alliances well in advance of FDA hearings; Advanced Magnetics has not. An agreement with Bristol-Myers Squibb fell apart in 1994, when Bracco acquired Squibb Diagnostics, and Advanced Magnetics got the rights to Combidex back, along with phase I results.

“We took over the whole development of the product, which was extremely complicated and expensive,” Goldstein said.

In these early trials, verification that a Combidex-enhanced MRI was accurately recording the cancer depended on histological results from the lymph node. Complicating the clinical research was the need to document that the removed lymph node was indeed the one imaged on the MR scan. Another problem was patient attrition: Of the 154 patients recruited for the definitive phase III trials, 20 did not go to surgery because the physicians believed so strongly in the contrast-enhanced MRI results that they deemed surgery unnecessary.

“Clinicians are not supposed to make clinical judgments based on experimental drugs, but as they get comfortable with the drugs, they do,” Goldstein said.

Now he and others at Advanced Magnetics are looking for their reward after a decade of hard work. Goldstein plans to use the next six months and the impending FDA review to stir interest among potential partners in striking a deal. Discussions with several candidates are under way, he said. There is no word yet on the terms being discussed, but if the past is any guide, FDA approval could bring a multimillion-dollar milestone payment to Advanced Magnetics from its new partner.