Washington Editor

GTx Inc. advanced its lead candidate, Acapodene (toremifene), into a second pivotal development program for prostate cancer.

A Phase III trial now is under way to test the compound's ability to prevent the disease in men at high risk. The U.S.-based, multicenter, double-blinded, placebo-controlled study is enrolling patients with high-grade prostatic intraepithelial neoplasia (PIN), the precancerous lesion in prostate cancer. They are being randomized into two treatment groups: 20 mg Acapodene or placebo.

The study's primary endpoint is the incidence of prostate cancer.

"What we're doing is actually something a little different from others in that we're going after high-risk men," GTx Vice Chairman and CEO Mitchell Steiner told BioWorld Today. "This Phase III represents the culmination of the basic science and clinical development that takes us up to this pivotal point."

He noted that other prevention studies are set up to exclude men with high-grade PIN, the very patients at which Acapodene is aimed. GTx's study will include 1,200 patients, and is proposed to last about 18 months.

The Memphis, Tenn.-based company is continuing to hammer down an exact protocol through the FDA's special protocol assessment process and has received initial comments from the agency on a preliminary review of the SPA. Steiner, who said GTx next plans to address those comments and resubmit a revised SPA, noted that the FDA's dialogue included no clinical-hold issues, so the company got the study going.

"The patients will get biopsied," he said, adding that the SPA process is designed to clarify an endpoint on which an approval could be based. "The endpoint is prostate cancer incidence, not whether or not the premalignant region goes away."

PIN is detected in about 9 percent of patients who undergo prostate biopsies, GTx said, and prostate cancer is found in about 30 percent to 70 percent of high-grade PIN patients within one year of diagnosis. Also, 45 percent to 80 percent of high-grade PIN patients get the disease within five years.

Prior findings, from a one-year Phase IIb study in 514 men with high-grade PIN, showed that Acapodene cut the cumulative prostate cancer risk to 24.4 percent at one year, compared to 31.2 percent for placebo. (See BioWorld Today, July 19, 2004.)

Acapodene, which binds and selectively modulates the estrogen receptor, already is in Phase III testing for the treatment of side effects such as skeletal fractures that result from androgen-deprivation therapy for advanced prostate cancer. The two-year study is expected to enroll 1,200 patients. (See BioWorld Today, Nov. 11, 2003.)

"We expect the trial to be completely enrolled by the third quarter of this year," Steiner said. "If it all happens as expected, we're looking at filing [a new drug application] in the second half of '07."

Also, the drug already is marketed by GTx for breast cancer under the trade name Fareston. The company has a license to U.S. rights from Orion Corp., of Espoo, Finland, to develop, market and distribute the small molecule's active ingredient in all indications.

All forms of the compound come in different doses: 20 mg for preventing prostate cancer, 60 mg for breast cancer and 80 mg for prostate cancer side effects.

"We've taken it this far, but we're not dummies," Steiner said. "We see ourselves as being in the urology and medical oncology specialty sales business, but clearly either one of these indications can go outside of that. We're U.S.-based and just don't have the breadth yet to go international, so at some point we'll be looking for a licensing and marketing partner for the rest of the world, and outside urology and medical oncology."

Beyond Acapodene, GTx's other clinical programs are related to therapeutics for men's health conditions. Its drug discovery and development activities are focused on small molecules that selectively modulate the effects of estrogens and androgens.

In concert with Ortho Biotech Products LP, a subsidiary of Johnson & Johnson, of New Brunswick, N.J., the company is developing andarine, a selective androgen receptor modulator (SARM) expected to enter a Phase II trial for cancer cachexia this year. Also, GTx is developing its own SARM, ostarine, for andropause and other conditions related to aging, such as sarcopenia. Its pipeline also includes a pair of preclinical product candidates, prostarine for benign prostatic hyperplasia and andromustine for hormone-refractory prostate cancer.

On Wednesday, GTx's stock (NASDAQ:GTXI) gained 27 cents to close at $12.78.

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