Results of Studies with TheraTech Testosterone Systems for Treatment of HIV-Infected Men and Women with Testosterone Deficiencies Presented at Endocrine Society Conference

Business Wire, June 30, 1998

PHILADELPHIA and SALT LAKE CITY--(BW HealthWire)--June 30, 1998-- The results from two studies evaluating transdermal testosterone replacement in HIV-infected individuals were reported at the recent Endocrine Society conference in New Orleans.

One study reported the use of Androderm(R) in HIV-infected men with low testosterone levels; the second study reported the use of a new experimental testosterone patch in HIV-infected women with the AIDS wasting syndrome.

ANDRODERM TESTOSTERONE REPLACEMENT STUDIES IN HIV-INFECTED MEN

The effects of testosterone administration in HIV-infected men using Androderm -- a transdermal system for testosterone replacement therapy in men with conditions associated with a deficiency or absence of endogenous testosterone developed by TheraTech Inc. (NASDAQ:THRT) and marketed in the U.S. by SmithKline Beecham (NYSE:SBH) -- was evaluated by a team of researchers headed by Dr. Shalender Bhasin, Professor of Medicine at UCLA and Charles R. Drew University of Medicine and Science.

According to Dr. Bhasin, "Testosterone deficiency is a common and significant problem in HIV-infected men. It also is a contributory factor to the AIDS wasting syndrome, a debilitating loss of lean muscle mass leading to physical weakness and fatigue in these patients."

The 12-week placebo-controlled study, funded by SmithKline Beecham, evaluated the effects of physiological testosterone replacement on lean-body mass, muscle strength, body weight, quality of life and HIV-disease markers in HIV-infected men ages 18 to 60 with low testosterone levels who were ambulatory and stable.

Patients were randomly assigned to either a placebo group (n=21) or active Androderm group (n=20). Two 2.5 mg Androderm patches were applied by each patient every 24 hours.

While the results of the study showed there were no statistical differences between the Androderm group and the placebo group, there was a 1.34 kg increase in lean-body mass in the Androderm group and no change in lean-body mass in the placebo group. There was a greater reduction in fat mass in the Androderm group than in those receiving placebo.

Total body weight did not change in either group. Changes in quality of life scores did not correlate with testosterone treatment, however, in the subcategory of role limitations due to emotional problems, the Androderm group improved significantly compared to the placebo group. Plasma HIV-copy number, CD4+ and CD8+ T-cell counts, and serum PSA and plasma lipids did not significantly change in either group.

Side effects of the treatment were limited to local skin reactions from the patches for both the placebo and Androderm patients. Androderm is contraindicated in women. Like all androgens, Androderm is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate.

Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma. Edema may be a serious complication in patients with pre-existing cardiac, renal or hepatic disease. As with all androgen therapies, PSA, hematocrit, liver function, hemoglobin and total cholesterol should be checked periodically.

"Our study demonstrated that physiologic testosterone replacement can be safely achieved in HIV-infected men using Androderm," Dr. Bhasin said.

"While Androderm is not approved for treating wasting syndrome, the patients treated with Androderm experienced on average a three pound gain in lean body mass, a decrease in body fat and an increase in red blood cells. Further studies are needed to determine if testosterone replacement therapy can produce clinically meaningful changes in muscle function and disease outcome in HIV-infected men."

EXPERIMENTAL TESTOSTERONE PATCH STUDY IN HIV-INFECTED WOMEN

TheraTech also is developing a transdermal testosterone system for women with testosterone deficiency. The effects of testosterone replacement, at doses appropriate for women, in the treatment of AIDS wasting in females was reported by Dr. Steven K. Grinspoon, assistant professor of medicine at the Harvard Medical School and Massachusetts General Hospital (MGH).

Although HIV disease is increasing rapidly among women, no prior studies have investigated gender-based therapeutic strategies for treating the AIDS wasting syndrome among this population.

"We previously have shown that women with AIDS have decreased testosterone levels, and we suspected that this deficiency may contribute to the wasting syndrome," Dr. Grinspoon stated. "Our MGH research team assessed the effects of testosterone replacement therapy in women with AIDS wasting syndrome during a 12 week, placebo-controlled study using TheraTech's experimental transdermal testosterone patch for women.

"This was the first investigation of testosterone administration in women with AIDS wasting," Dr. Grinspoon pointed out. "The testosterone administration was well tolerated and we observed a significant weight gain and an overall improvement in several aspects of the patients' quality of life. Further studies will be needed to confirm the promising findings of this initial study," he concluded.