By Kim Coghill

Washington Editor

SILVER SPRING, Md. ¿ Guilford Pharmaceuticals Inc.¿s brain cancer wafer Thursday won recommended approval for a second indication, which would give the Baltimore-based company a major share of that disease market.

The FDA¿s Oncologic Drugs Advisory Committee (ODAC) voted 8 to 5 in favor of using the Gliadel Wafer (carmustine) for newly diagnosed malignant glioma, a fatal form of brain cancer. In 1997, the wafer was launched for recurrent glioblastoma multiforme (GBM), and so far this year it has generated $13.8 million in North American sales. The FDA makes the final decision on regulatory approval and is not bound by the committee¿s recommendation.

According to research notes released by Andrew Gitkin, senior analyst with UBS Warburg in New York, the Gliadel Wafer has no visible competition on the market. Expansion of the label would increase Guilford¿s patient potential from the current 3,000 to the entire 12,000 patient population in North America, Gitkin said. Financially, the wafer ¿ Guilford¿s first product on the market ¿ is expected to generate $80 million per year by the end of decade in North America.

But the committee chairman, Stacy Nerenstone, associate clinical professor, Oncology Associated PC, Helen & Harry Gray Cancer Center at Hartford Hospital in Hartford, Conn., called the wafer a placebo. ¿I¿m concerned that we have an intervention that has a borderline significance to prolong survival and we have no clinical statistics to show that it is meaningful. I¿m concerned that we are going to approve a placebo.¿

Nerenstone¿s comments were based on Guilford¿s application that included a randomized, placebo-controlled trial of 240 patients suffering from newly diagnosed malignant glioma. The endpoint was survival.

At the end of trial, 79 patients (78.2 percent) in the Gliadel group died and 85 patients (80.2 percent) in the placebo group died. The median survival for Gliadel patients was 13.9 months compared to 11.6 months for placebo patients.

The FDA criticized the study for being too small and showing only modest statistical significance

Others agreed that the study was weak and marginal, but said the drug is not a placebo as it is an approved product already on the market.

The wafer works by delivering chemotherapy directly to the site of the tumor, minimizing drug exposure to other parts of the body. The product is a small, white, dime-sized wafer comprised of biodegradable polymer incorporating the chemotherapeutic agent BCNU (carmustine). Up to eight wafers can be implanted in the cavity created when a surgeon removes a brain tumor. There, the wafers slowly erode, releasing BCNU directly at the tumor site in high concentrations.

The first indication was approved based on a study of 222 patients undergoing surgery for GBM. Use of the wafer increased survival at six months by more than 50 percent. Several months following FDA clearance of the first indication, Guilford and Aventis Pharma, the pharmaceutical company of Aventis SA, entered an agreement to market and distribute the wafer. The agreement concluded about a year ago when Guilford regained all the rights. (See BioWorld Today, Oct. 25, 2000.)

Guilford faced another change of events earlier this year when Amgen Inc., of Thousand Oaks, Calif., dropped development of a Parkinson¿s disease product the companies were developing. The multimillion-dollar deal ended about a month after a Phase II trial of neuroimmunophilin ligand missed all its endpoints. (See BioWorld Today, Aug. 22, 1997; July 27, 2001; and Sept. 20, 2001.)

Guilford regained the technology in that deal and is expected to develop the product on its own. Gitkin¿s office said the company likely will make an announcement on that product in the second quarter of next year.

Analysts expect Guilford¿s next product, Aquavan (an injection for treatment of chronic and acute neurodegenerative disorders), to enter the market by 2004.