First Fracture Prevention Study In Men Receiving ADT For Prostate Cancer Presented At AACR Annual Meeting

Main Category: Prostate / Prostate Cancer
Also Included In: Cancer / Oncology;  Bones / Orthopaedics
Article Date: 17 Apr 2008 - 16:00 PDT

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GTx, Inc. (NASDAQ: GTXI) announced that results of the Phase III ADT clinical trial evaluating toremifene citrate 80 mg for the treatment of multiple side effects of androgen deprivation therapy (ADT) in men who have advanced prostate cancer were presented during a late breaking oral session at the 2008 Annual Meeting of the American Association for Cancer Research (AACR) in San Diego. Results of the Phase III ADT clinical trial demonstrate that toremifene citrate 80 mg compared to placebo built bone and prevented fractures, reduced hot flashes, and treated other estrogen related side effects of ADT.

ADT, the most common treatment for advanced prostate cancer, is a form of hormone therapy that works by reducing testosterone and estrogen. While it is successful in stopping the progression of prostate cancer, it can result in multiple estrogen related side effects, including bone loss and increased risk of fractures, hot flashes, adverse lipid changes and increased cardiovascular risk, and gynecomastia (breast pain). Studies have shown that men on ADT are three times more likely to experience a fracture than postmenopausal women, and that when they develop a fracture, their median survival rate decreases by more than three years.

"As a medical oncologist treating prostate cancer patients, I have seen firsthand how the serious side effects of ADT not only have an impact on a man's quality of life but can also be life threatening," 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 Investigator of the Phase III ADT clinical trial. "There are no medicines approved to treat side effects of ADT. The results of the Phase III ADT clinical trial are exciting, as they demonstrate that toremifene citrate 80 mg prevents fractures and treats other side effects of ADT."

About the study

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

Primary endpoint

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, patients receiving toremifene citrate 80 mg had approximately a 53 percent reduction in new morphometric vertebral fractures compared to placebo (p=0.03).

Other endpoints

Patients treated with toremifene citrate 80 mg compared to placebo had statistically significant increases in bone mineral density in the lumbar spine, hip, and femur skeletal sites (each p<0.001). Toremifene citrate 80 mg treatment also resulted in a decrease in total cholesterol (p=0.011), LDL (p=0.018), and triglycerides (p<0.0001), and an increase in HDL (p=0.001). There were also statistically significant improvements in gynecomastia (p=0.003). In patients experiencing 6 or more hot flashes per day at baseline who were not being treated with megestrol acetate (Megace®), toremifene citrate 80 mg was shown to reduce the number of hot flashes by an average 4.7 hot flashes per day compared to placebo patients who had a reduction of 1.6 hot flashes per day (p=0.03).

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 greater than 80 years, history of VTE, recent surgical procedure and immobilization. Excluding high risk patients over the age of 80 years and with a history of VTEs, the VTEs were 7 (1.3 %) in the toremifene citrate 80 mg treated group and 4 (1.0%) in the placebo group (p=0.38), and toremifene citrate 80 mg compared to placebo demonstrated an 80% reduction in new morphometric vertebral fractures (p=0.002).

There was no difference in prostate specific antigen (PSA) progression in patients treated with toremifene citrate 80 mg when compared with patients receiving placebo.

About GTx

GTx, Inc., headquartered in Memphis, Tenn., is a biopharmaceutical company dedicated to the discovery, development, and commercialization of small molecules that selectively target hormone pathways to treat cancer, osteoporosis and bone loss, muscle wasting and other serious medical conditions.

GTx is developing ACAPODENE® (toremifene citrate), a selective estrogen receptor modulator, or SERM, in two separate clinical programs in men: first, a pivotal Phase III clinical trial evaluating toremifene citrate 80 mg for the treatment of serious side effects of androgen deprivation therapy for advanced prostate cancer, and second, a pivotal Phase III clinical trial evaluating toremifene citrate 20 mg for the prevention of prostate cancer in high risk men with high grade prostatic intraepithelial neoplasia, or PIN.

GTx licensed from Orion Corporation the rights to toremifene citrate for all indications worldwide, except breast cancer outside the United States. In 2006, GTx and Ipsen Group entered into a development and collaboration agreement for toremifene citrate in all indications except breast cancer for Europe and the Commonwealth of Independent States (CIS). Ipsen is the leading marketer of ADT (triptorelin) in Europe. Under the agreement, Ipsen will be responsible for filing for marketing approval with regulatory authorities and commercializing toremifene citrate in Europe and CIS. GTx will file for marketing approval and, if approved, plans to commercialize toremifene citrate 80 mg in the United States.

GTx has formed a strategic collaboration with Merck & Co., Inc. for the development and global commercialization of selective androgen receptor modulators, or SARMs, a new class of drugs with the potential to treat a variety of indications associated with muscle wasting and bone loss, including frailty or sarcopenia, muscle wasting associated with chronic diseases, osteoporosis, and cancer cachexia. GTx also has announced that it is developing its preclinical compounds, GTx-758, an oral LH inhibitor for advanced prostate cancer, and GTx-878, an estrogen receptor beta agonist for the treatment of benign prostatic hyperplasia and chronic prostatitis.

Forward-Looking Information is Subject to Risk and Uncertainty

This press release contains forward-looking statements based upon GTx's current expectations. Forward-looking statements involve risks and uncertainties. GTx's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the risks that (i) GTx and its collaboration partners will not be able to commercialize their product candidates if clinical trials do not demonstrate safety and efficacy in humans; (ii) GTx may not able to obtain required regulatory approvals to commercialize product candidates; (iii) clinical trials being conducted by GTx and its collaboration partners may not be completed on schedule, or at all, or may otherwise be suspended or terminated; and (iv) GTx could utilize its available cash resources sooner than it currently expects and may be unable to raise capital when needed, which would force GTx to delay, reduce or eliminate its product development programs or commercialization efforts. You should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release. GTx's annual report on Form 10-K filed March 11, 2008 contains under the heading, "Risk Factors," a more comprehensive description of these and other risks to which GTx is subject. GTx expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

GTx, Inc.