By Mary Welch

Neurocrine Biosciences Inc. and Medtronic Inc. entered into a collaborative arrangement to clinically evaluate a drug and delivery system for treating malignant brain tumors. In addition, San Diego-based Neurocrine Biosciences released successful Phase I data on IL-4 Fusion Toxin (NBI-3001), the drug which will be used in the collaboration.

No financial terms were disclosed. The two companies will clinically evaluate the drug for direct delivery to the brain using Minneapolis-based Medtronic's SynchroMed infusion system. This system consists of a programmable, implantable drug pump and catheter that delivers medication directly to the site, where the drug can be most effective. Joint clinical studies should begin in the second half of 1999.

"What we're doing with this collaboration is working to find a way of getting a big molecule to penetrate the brain," said Stephen Marcus, senior vice president of clinical and regulatory affairs at Neurocrine Biosciences. "The problem with most surgery and radiation is that it is focused on the tumor in one location. The tumor cells are killed in the center, but on the outskirts of the tumor, they aren't. That's been why the cancer reoccurs in 99.9 percent of the cases. Ultimately, it leads to death. The chemotherapy isn't terribly potent."

NBI-3001 is a "highly toxic, highly potent molecule," Marcus said. "We believe that it will spare the normal cells. With the delivery system, we will provide a potent infusion into the brain. We will saturate the brain's hemisphere, maybe both, with the drug. We'll ultimately sterilize the brain from brain tumor cells."

The Phase I results, which were presented earlier this month at the Society for Neuro-Oncology meeting in San Francisco, concluded that IL-4 Fusion Toxin produced no evident systemic or neurological toxicities.

In the study, NBI-3001 was infused directly into brain tumors and surrounding parenchyma via convection catheter delivery in nine patients with recurrent malignant brain tumors. Of the nine patients treated, five showed evidence of necrosis (tumor cell death) in major sections of the tumor by MRI, PET and MR-SPEC scanning.

The IL-4 Fusion Toxin binds with high affinity to IL-4 receptors, which are numerous on malignant glioblastoma cells but are not found on normal brain cells. NBI-3001 is designed to bind and destroy malignant cells without harming normal ones.

"If it works, and it has shown promising results, it could be a very important advance in the treatment of brain tumors and an important step forward in other diseases as well," Marcus said.

The company has started a multicenter, multinational Phase I/II study in 30 patients with recurrent glioblastoma. The primary endpoints are safety, tumor regression and progression-free survival. The drug will be administered by infusion by way of a special catheter, which will permit diffusion of NBI-3001 into the tumor and surrounding parenchyma of the brain.

Neurocrine has five compounds in clinical development for central nervous system disorders. In addition to NBI-3001, its CRF receptor antagonist is in Phase II development with Janssen Pharmaceutica, of Olen, Belgium, for anxiety/depression. With partner Novartis Pharmaceuticals, of Basel, Switzerland, Neurocrine is conducting a second Phase II trial of its APL compound in patients with multiple sclerosis. The company is also conducting a Phase I trial of NBI-34060 for insomnia. Neuroscience Pharma Inc., Neurocrine's affiliate, recently completed a Phase III trial of its neurosteroid compound for Alzheimer's disease.

Medtronic's stock (NYSE:MDT) closed Wednesday at $69.687, unchanged. Neurocrine Biosciences' stock (NASDAQ:NBIX) closed Wednesday at $6.937, unchanged. *

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