By Jim Shrine

Special To BioWorld Today

Aiming to fill a longstanding medical need, Pharmacyclics Inc. on Friday began a pivotal Phase III trial of its lead product, the radiation sensitizer Gd-Tex, in patients with metastatic brain cancer.

Sunnyvale, Calif.-based Pharmacyclics plans to enroll 425 patients at 30 centers in the U.S., Canada and Europe. Gd-Tex will be used along with standard whole-brain radiation therapy and compared against radiation therapy alone. The primary endpoint is survival.

Peter Ginsberg, senior research analyst with Piper Jaffray Inc., in Minneapolis, said he was "very optimistic" about Gd-Tex's prospects.

"The radiation oncology clinical community has been seeking a radiation sensitizer for upwards of 50 years," Ginsberg told BioWorld Today. "Currently, there is no approved radiation sensitizer. Gd-Tex has an opportunity to fill that void."

Gd-Tex, or gadolinium texaphyrin, is a synthetic molecule that has been shown to selectively accumulate in cancer cells. When activated by radiation therapy, the molecule in prior studies has appeared to increase damage to cancerous cells without increasing damage to normal cells.

A comparison to historical controls in Phase I and Phase Ib/II trials showed a statistically significant improved response rate and prolonged survival, the company said.

Study Qualifies Product For Fast-Track Review

The Phase III study will be prospectively randomized. The treatment group will receive 10 intravenous injections of Gd-Tex prior to 10 daily fractions of radiation therapy. Patients will be followed for at least six months or until death. Secondary endpoints include tumor response, time to neurologic progression and neurocognitive function.

Since survival is the primary endpoint, the Phase III trial qualifies for fast-track review with the FDA. Should Gd-Tex yield positive results, the Phase III study would be the only study necessary for the company to apply for marketing approval.

Ginsberg estimated such a filing at the end of 1999 or early 2000, with sales in 2001. Although Gd-Tex would be approved first for brain cancer, Ginsberg said, he expects it to be used in "a number of other tumors."

Gd-Tex works by absorbing free electrons generated during irradiation, effectively prolonging and magnifying the destructive action of highly reactive hydroxyl free radicals. Free radicals are cytotoxic and destroy the surrounding cancerous tissue.

In August, the National Cancer Institute (NCI) began two Phase I studies of Gd-Tex for the treatment of primary brain tumors. Additional NCI trials may be run using the radiation sensitizer to treat other cancers, including tumors of the head and neck, lung, pancreas and prostate gland.

Pharmacyclics has two other drug candidates from the texaphyrin class in the clinic. Both are lutetium texaphyrins, rather than gadolinium. Lutrin is in Phase II studies for the photodynamic treatment of recurrent breast cancer. Antrin is in Phase I studies for the photoangioplasty of atherosclerosis.

The company went public in February with a 2 million share offering at $21.75 per share, resulting in net proceeds of $40.8 million. It had $70.4 million in cash on June 30, with a net loss of $9.7 million for the fiscal year that ended June 30.

Pharmacyclics' stock (NASDAQ:PCYC) closed Friday at $15.375, down $0.375. *