GTx, Inc. announced that in a phase II, open label, pharmacokinetic-pharmacodynamic clinical trial, GTx-758, an oral selective estrogen receptor alpha agonist being developed to treat advanced prostate cancer, suppressed serum total testosterone to castrate levels, increased serum SHBG (sex hormone binding globulin), and markedly reduced serum free testosterone in healthy male volunteers.

60 healthy male volunteer subjects were randomized to receive one of three oral daily doses of GTx-758 (600 mg, 1000 mg or 1500 mg) until the earlier of achieving medical castration or 56 days. Medical castration (levels of serum total testosterone <50 ng/dL) was achieved in subjects receiving both the 1000 mg and 1500 mg treatment.

In the 1500 mg group, compliance with treatment was confirmed by statistical analysis of trough plasma concentrations. The percentage of treatment compliant subjects receiving 1500 mg of GTx-758 who achieved medical castration was comparable to rates of castration observed with LHRH treatment. Castration was achieved in these subjects within three weeks. A surge in serum testosterone levels was not observed in subjects treated with any dose of GTx-758. GTx-758 was well tolerated and no serious adverse events were reported in the study.

"Achieving medical castration in healthy young male volunteers, a population in whom it is more difficult to reduce testosterone to castration levels, provides the scientific evidence of the pharmacologic mechanism of action of GTx-758 and its potential as a new hormonal treatment for advanced prostate cancer," said Mitchell S. Steiner, MD, CEO of GTx.

Additionally, GTx-758 increased serum SHBG, a protein which binds to testosterone, thus further reducing serum free testosterone to levels lower than what is reported to be achievable with LHRH treatment. Free testosterone is the form of testosterone which prostate cancer cells utilize for growth.

"The ability of GTx-758 to reduce serum free testosterone well below levels achieved with standard LHRH therapy may result in improved tumor control in first line therapy as well as allow for the use of GTx-758 for second line hormonal manipulation in men with advanced prostate cancer," said Ronald A. Morton, Jr., Chief Medical Officer of GTx.

In addition to serum levels of total testosterone, SHBG, and free testosterone, GTx also measured luteinizing hormone, follicle stimulating hormone, and bone turnover markers. GTx expects to report full results from this clinical trial at upcoming medical meetings.

In 2011, GTx is planning to initiate additional clinical trials evaluating GTx-758 for first line treatment in men with advanced prostate cancer and second line treatment in men with prostate cancer who have failed LHRH treatment or surgical orchiectomy.

The standard of care for men with advanced prostate cancer is androgen deprivation therapy (ADT) commonly achieved surgically via bilateral orchiectomy or medically via injection of an LHRH analog. These therapies are associated with symptomatic side effects that can reduce treatment compliance (hot flashes) and result in increased morbidity (bone loss and increased risk of clinical fragility fractures).

As a selective estrogen receptor alpha agonist, GTx-758 has the potential to achieve medical castration by feedback inhibition of the pituitary and hypothalamus without bone loss and hot flashes.

In 2009, GTx evaluated GTx-758 in two Phase I clinical trials. In a single ascending dose study in 96 subjects, GTx-758 was well tolerated and demonstrated a pharmacokinetic profile compatible with daily oral dosing. In a 14 day multiple ascending dose study in 50 subjects, GTx-758 was well tolerated and demonstrated the ability to reduce testosterone and to increase SHBG.

GTx, Inc., headquartered in Memphis, Tennessee is a biopharmaceutical company dedicated to the discovery, development, and commercialization of small molecules that selectively target hormone pathways for the treatment and prevention of cancer, the treatment of side effects of anticancer therapy, cancer supportive care, and other serious medical conditions.