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Toremifene Citrate Reduced Vertebral Fractures and Met Other Key Endpoints

MEMPHIS, Tenn. -- GTx today announced Phase III clinical data for toremifene citrate 80 mg, the Company’s investigational therapy for the treatment of multiple side effects of androgen deprivation therapy (ADT) for advanced prostate cancer. Results show that toremifene citrate 80 mg reduced vertebral fractures and met other key endpoints, including bone mineral density, lipid profiles, and gynecomastia.

Based on these findings, GTx plans to file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) by the summer of 2008. In addition, GTx plans to present the full data set at an upcoming medical meeting.

“The toremifene citrate 80 mg Phase III ADT clinical trial is the first fracture prevention study in men receiving ADT for prostate cancer. The study confirms that men receiving ADT are at high risk for fractures. The rate of vertebral fracture in the placebo group in this study was about 10 times greater than that expected for men of a similar age not receiving ADT, as reported in other studies,” said Matthew R. Smith, MD, PhD, Director, Genitourinary Medical Oncology, Massachusetts General Hospital Cancer Center, Associate Professor of Medicine at Harvard Medical School, and Lead Principal Investigator of the Phase III ADT clinical trial.

“Androgen deprivation therapy is the cornerstone treatment for men with advanced prostate cancer, but has been associated with serious side effects. The results from this exciting study demonstrate that toremifene citrate 80 mg reduced fractures and other side effects in men taking ADT,” added Dr. Smith.

About the Disease
Androgen deprivation therapy is the most common treatment for advanced prostate cancer, used in approximately 800,000 men. ADT (e.g., leuprolide/triptorelin injections) is hormone therapy that works by reducing testosterone and estrogen. This may result in multiple estrogen related side effects, including bone loss and fractures, hot flashes, lipid changes and increased cardiovascular risk, and gynecomastia. Studies have shown that men on ADT are at risk for fractures, and ADT patients who develop a fracture have a 39 month shorter median survival. ADT has also been associated with increased risk of cardiovascular disease and death. There are no drugs approved by the FDA to treat multiple side effects of ADT for prostate cancer. Men with prostate cancer of a similar age who are not on ADT have a vertebral fracture rate of approximately 0.3% over two years.

About the Study
The two year double-blind, placebo-controlled study randomized 1,389 ADT patients at approximately 150 clinical sites in the United States and Mexico. The primary endpoint was new morphometric vertebral fractures read by an independent third party. Other key endpoints included bone mineral density, lipid changes, hot flashes, and gynecomastia.

Fracture endpoints
In a modified intent to treat analysis which included all patients with at least one evaluable study radiograph and a minimum of one dose of study drug or placebo, toremifene citrate 80 mg demonstrated a 50% reduction in morphometric vertebral fractures (p In prespecified subset analyses, in study patients who were greater than 80% treatment compliant, toremifene citrate 80 mg reduced vertebral morphometric fractures by 61% (p=0.017). When study patients who had greater than 7% bone loss at one year and new morphometric vertebral fractures were considered as treatment failures, toremifene citrate 80 mg compared to placebo demonstrated a 56% reduction (p=0.003).

Other key endpoints
Patients treated with toremifene citrate 80 mg compared to placebo demonstrated statistically significant increases in bone mineral density in the lumbar spine, hip, and femur skeletal sites (each site demonstrating p Safety
Toremifene citrate 80 mg had a favorable safety profile and was well tolerated. Among the most common adverse events that occurred in over 2% of study subjects were joint pain (treated 7.3%, placebo 11.8%), dizziness (treated 6.3%, placebo 5.0%), back pain (treated 5.9%, placebo 5.2%), and extremity pain (treated 5.0%, placebo 4.4%).

Venous thromboembolic events (VTE), which included both deep venous thrombosis and pulmonary embolism, were 17 (2.4 %) in the toremifene citrate 80 mg treated group and 7 (1.02 %) in the placebo group. The majority of VTEs occurred in men at high risk for a VTE including: age >80 years, history of VTE, recent surgical procedure and immobilization. In men without major risk factors for VTE, there were 3 VTE in the toremifene citrate 80 mg treated group and 2 VTE in the placebo group. The most significant VTE risk occurred in the first year of treatment. In year two, the VTE event rate in the toremifene citrate 80 mg treated group was similar to the rate observed in the placebo group.

“GTx has successfully reached an important corporate milestone event by meeting the primary and key secondary objectives of the Phase III ADT clinical trial,” said Dr. Mitchell Steiner, Chief Executive Officer of GTx. “We now can move forward with our plans to prepare and submit the NDA for toremifene citrate 80 mg.”

Source: GTx

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