West Coast Editor

With a pivotal Phase III trial under way with Acapodene to treat complications of prostate cancer treatment, GTx Inc. offered new and encouraging data from Phase IIb study with the drug to prevent the disease in high-risk men.

Depending on the outcome of talks with the FDA, a planned confirmatory Phase III study in the second indication could finish about the same time as the other study, said Marc Hanover, co-founder, president and chief operating officer of GTx.

"Both of them, we feel, are very valuable indications from a market-opportunity perspective, but clearly the prevention of prostate cancer in high-risk men is a very big draw," he said.

Memphis, Tenn.-based GTx's stock (NASDAQ:GTXI) closed Friday at $9.04, down 15 cents. Top-line data already had been disclosed.

The one-year Phase IIb study in 514 men with high-grade prostatic intraepithelial neoplasia (PIN) had as its primary endpoint the incidence of prostate cancer. Results showed the nonsteroidal selective estrogen receptor modulator cut the cumulative risk at one year in the 20-mg Acapodene arm to 24.4 percent, as compared to 31.2 percent with placebo.

For comparison, GTx pointed to results in a breast cancer prevention trial with tamoxifen, which prevented 0.33 cancers for every patient per year. Acapodene prevented 6.8 cancers for every 100 patients treated in the Phase IIb trial.

What's more, the outcome suggested that the longer men with high-grade PIN are treated, the greater the likelihood their prostate-cancer risk is reduced. Patients in the study who had a negative prostate cancer biopsy after six months of treatment had a risk reduction of 48 percent after a full 12 months of treatment (p=0.045).

Those who did develop prostate cancer while being given Acapodene had no difference in tumor grades - with a trend toward even lower grades compared to those patients who developed prostate cancer during the study while on placebo.

The drug was well tolerated, too. Serious adverse events with the drug were comparable to placebo (7 percent and 11 percent, respectively), with the most common adverse events turning out similar to placebo: headache (2 percent and 6 percent), fatigue (5 percent and 3 percent), hot flashes (2 percent and 3 percent), and nausea (1 percent and 4 percent).

"The safety profile was excellent," Hanover said.

PIN typically is discovered after an internist finds a patient's prostate specific antigen is elevated, or notes an abnormality via digital rectal exam. A biopsy might confirm the suspicion regarding the pre-malignant lesions - 30 percent of which will become cancer within a year, and 80 percent within five years.

Data from the Phase IIb trial were presented at the Fourth International Prostate Cancer Congress on Grand Bahama Island in the Bahamas.

The ongoing Phase III trial of Acapodene is ongoing to test the drug for reducing skeletal fractures and other complications of androgen deprivation therapy in men with prostate cancer. The 24-month, placebo-controlled study is expected to enroll 1,200 patients. (See BioWorld Today, Nov. 11, 2003.)

"The only thing I can tell you is our enrollment is going as planned," Hanover said of that trial. "We're looking to get 100 sites up. Right now we have about 70." Target date for complete enrollment is the third quarter of next year.

GTx, which focuses on men's health, licensed rights to develop, market and distribute toremifene citrate worldwide for prostate cancer from Finland-based Orion Corp. The estrogen-blocking drug already is approved for preventing breast cancer, although "it's not big in sales," Hanover told BioWorld Today. "It works, but it came out just behind tamoxifen," sold by London-based AstraZeneca plc as Nolvadex.

Behind the lead product Acapodene, GTx has andarine and other backup compounds with its partner, Ortho Biotech Products LP, a subsidiary of New Brunswick, N.J.-based Johnson & Johnson. Andarine is expected to enter a Phase II trial for cancer cachexia this year. GTx retains all rights to the rest of its SARM program, which includes ostarine, prostarine and andromustine. (See BioWorld Today, March 18, 2004.)

Those preclinical compounds are "moving along very nicely," Hanover said, adding that the company will have more news about their development in the first quarter.

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