Just weeks after raising nearly $70 million, cancer drug developer NeoPharm Inc. said the FDA signed off on plans for a pivotal study of its investigational brain cancer drug.

The Lake Forest, Ill.-based company and the agency reached an agreement under the special protocol assessment (SPA) process for a Phase III trial of IL13-PE38QQR, a tumor-targeting product for the first recurrence of glioblastoma multiforme. Under SPA guidelines, if the trial meets certain pre-specified results, those findings may serve as the primary basis for efficacy in supporting an eventual biologics licensing application.

Just two weeks ago, NeoPharm said it planned to use proceeds from a $68.4 million public offering to advance the experimental cancer agent into the final stages of development. (See BioWorld Today, Jan. 23, 2004.)

Called PRECISE (Phase III Randomized Evaluation of Convection Enhanced Delivery of IL13-PE38QQR with Survival Endpoint), the trial is designed to evaluate IL13-PE38QQR in head-to-head comparison with Gliadel Wafer (polifeprosan 20 with carmustine implant). More specifically, PRECISE will evaluate the overall survival, drug safety and quality of life of patients receiving IL13 to those receiving Gliadel in treating first recurrent glioblastoma multiforme following surgical tumor removal. Its primary endpoint is to show a 50 percent improvement over Gliadel, which was developed by Baltimore-based Guilford Pharmaceuticals Inc.

"Gliadel is what is currently used by everybody," Paul Arndt, NeoPharm's corporate communications manager, told BioWorld Today. "Its current median survival rate is 28 weeks, so that's our control group. The goal of the PRECISE trial is to show 42 weeks of survival over Gliadel's 28 weeks."

PRECISE is designed to enroll 300 patients in multiple centers across North America, Europe and Israel. They will be randomized so that 200 receive IL13 via convection-enhanced delivery using catheters placed following the tumor's resection. The placement will occur a few days following the removal procedure, to allow the brain to shift, pushing the drug into the brain and cavity. The other 100 will receive Gliadel placed at the time of resection. NeoPharm said it expects to enroll initial patients within the next four to six weeks, with full enrollment lasting about 18 months.

The study could prove an early success if interim analyses prove the drug has hit built-in endpoints, allowing NeoPharm to begin filing the BLA.

At the same time, the FDA named the IL13 program to its new Continuous Marketing Application (CMA) Pilot 2 program. NeoPharm will work with the agency over the next several weeks to finalize an agreement on its participation in the exploratory program, which is designed to test the CMA concept during the investigational new drug phase of development to determine whether such activity can improve the efficiency of the drug development and review process and shorten review time. Under the CMA Pilot 2 program, the FDA and fast-track drug applicants will engage in scientific feedback and interactions during the IND phase of product development.

An orphan drug in the U.S. and Europe, IL13 also has fast-track status from the FDA. The compound is a recombinant protein made of a single molecule composed of two parts - a tumor-targeting molecule (IL13) and a cytotoxic agent (Pseudomonas exotoxin). Previous studies have shown that the cancer cell appears to receive IL13 and the attached cytotoxic agent, causing the cell's death as a result of the infusion of Pseudomonas exotoxin.

"It's very targeted and only kills the cancer cells, not the healthy brain tissue surrounding the area," Arndt said. Healthy brain cells do not appear to express IL13 receptors, and thus, are not believed to internalize Pseudomonas exotoxin.

NeoPharm has an exclusive license to the product from the agency and the National Cancer Institute in Bethesda, Md. Its development is being carried out under a Cooperative Research and Development Agreement in collaboration with the FDA's Center for Biologics Evaluation and Research.

Beyond IL13, the company' pipeline includes five Phase I/II products from its NeoLipid program. All are under evaluation for various cancers, including colorectal, lung, pancreatic, prostate, breast and ovarian.

On Friday, NeoPharm's stock (NASDAQNM:NEOL) gained 95 cents to close at $18.73.