By Kim Coghill

Washington Editor

Peregrine Pharmaceuticals Inc. in the next couple of months expects to start enrolling patients in a pivotal Phase III trial to evaluate Cotara, a treatment for recurrent glioblastoma multiforme.

Edward Legere, Peregrine¿s president and CEO, told BioWorld Today that the company and the FDA have finished meetings whereupon they agreed on the 24-month study design. Cotara is monoclonal antibody that carries the radioactive isotope Iodine-131 to the necrotic core of solid tumor cancers. Cotara is based on Peregrine¿s Tumor Necrosis Therapy (TNT), a class of therapeutic agents that acts by binding to dead and dying cells found in the tumor.

For Peregrine, a Tustin, Calif.-based company founded in 1983, entering Phase III trials for its lead product is a major achievement. The FDA has granted Cotara fast-track and orphan status for the unpartnered product.

¿One of the goals of the company was to be able to launch the Phase III for Cotara in brain cancer and we are doing that,¿ Legere said. ¿We view this as a major milestone ¿ we¿re on our way.¿

Legere said Cotara is a salvage therapy, likely useful in patients who already have undergone at least one round of surgery and treatment. ¿We put a 3-millimeter hole into the skull and insert two catheters into the tumor mass. Then we infuse the drug directly into the tumor. We are delivering an extremely high dose of radiation into the tumors. This is a localized treatment.¿

The Phase III study will have an open-label, randomized design comparing Cotara (131I-chTNT-1/B MAb) and temozolomide in patients with recurrent glioblastoma multiforme (GBM). Approximately 400 patients will be treated in the study upon first recurrence of GBM after receiving primary treatment for their disease. The study will be conducted in 70 sites across the U.S., Canada and Europe.

Preliminary reports of Phase II trials showed the overall median time to disease progression was 13.9 weeks. Comparatively, median time to progression for the historical control population was eight weeks.

Legere said survival data on the Phase II trials have not yet been published. Furthermore, he said the company does not intend to shut down Phase II trials, even as Phase III begins. ¿We will run Phase III at the same time. That way we can treat patients who have a third and fourth relapse.¿

With positive results, Legere hopes to file for regulatory approval in 2004. He said the antibody can be used for other cancers and currently is in Phase I studies for colorectal, pancreatic, liver, soft tissue sarcoma and biliary cancers.

Peregrine¿s announcement of Phase III trials in this deadly form of brain cancer comes a week after Baltimore-based Guilford Pharmaceuticals Inc. won recommended approval from the FDA¿s Oncologic Drugs Advisory Committee to use the Gliadel Wafer (carmustine) for newly diagnosed malignant glioma. In 1997, the wafer was launched for recurrent GBM. (See BioWorld Today, Dec. 7, 2001.)

According to the American Cancer Society, this year there will be up to 17,200 new cases and 13,100 deaths from brain and central nervous system cancers.

Oncolym, a Peregrine antibody for the treatment of advanced non-Hodgkin¿s B-cell lymphoma, is in Phase I/II trials. (See BioWorld Today, June 11, 2001.)

Peregrine¿s stock (NASDAQ:PPHM) closed Thursday at $3.02, down 23 cents.