FDA Approves GlaxoSmithKline's Avodart, The First Dual-Acting 5 Alpha-Reductase Inhibitor for Benign Prostatic Hyperplasia, BPH.

Business Editors

RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--Oct. 10, 2002

Avodart Improves Symptoms and Reduces Risk of Acute

Urinary Retention and the Need for

BPH-Related Surgery in Men with an Enlarged Prostate

The U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application for Avodart(TM) (dutasteride) for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve urinary symptoms, reduce risk of acute urinary retention (AUR) and reduce the risk of the need for BPH-related surgery.

Avodart, a second-generation 5 alpha-reductase inhibitor, is the first and only medicine to inhibit both the type 1 and type 2 enzymes responsible for the conversion of testosterone to DHT (dihydrotestosterone), the primary cause of prostate growth. Avodart's dual inhibition decreases levels of DHT by 90 percent at two weeks and 93 percent at two years.

By reducing DHT levels, Avodart reduces the size of an enlarged prostate. In clinical studies, this reduction in prostate volume was seen as early as one month with reductions continuing through treatment. Shrinking the enlarged prostate relieves urinary obstruction and improves urinary flow. Avodart also improves urinary symptoms and reduces the risk of AUR (the sudden complete inability to urinate) and BPH-related surgery, two potential long-term serious consequences of BPH. The pivotal phase III study data were published in this month's edition of the journal Urology.(1)

"With Avodart, we now have a medicine that reduces the production of DHT by more than 90 percent, helping to shrink the prostate," said Claus Roehrborn, MD, a principal trial investigator and professor and chairman of the Department of Urology at the University of Texas Southwestern Medical Center in Dallas, Texas. "By taking Avodart, patients can improve urinary symptoms and reduce their risk of suffering from acute urinary retention - where you suddenly can't urinate at all - or needing BPH-related prostate surgery."

BPH is one of the most common health problems in older men.(2) BPH often begins after age 50 and can progress and worsen as men age. More than half of men over age 60 experience BPH,(3) and by age 80, nearly 80 percent of men have the disease.(3)(4) In the United States alone, 375,000 hospital stays each year involve a diagnosis of BPH.(5)

BPH is a progressive disease in which the prostate gland surrounding the urethra enlarges.(6) As it grows, the prostate obstructs the urethra, the tube through which urine flows, causing urinary difficulties. BPH symptoms may interfere with normal activities and reduce the sense of well being.(7) Symptoms of BPH vary, but the most common involve urinary problems, such as a hesitant, interrupted weak stream; urgency and leaking or dribbling; and more frequent urination, especially at night.(5) In severe cases, the bladder and the kidney may become damaged.(5)

An enlarged prostate can continue to increase in size and may in severe cases lead to AUR and the need for BPH-related surgery.(6) A 60-year-old man with a 20-year life expectancy has a 23 percent risk of developing acute urinary retention.(8) Among men 60 years or older, with prostatic enlargement and obstructive symptoms, the 20-year probability of needing BPH-related surgery is 39 percent.(9)

To diagnose BPH, a physician will discuss urinary symptoms with a patient and conduct a digital rectal exam. A physician may also use a simple blood test that measures a protein called "prostate-specific antigen," or PSA. PSA is produced by the prostate, and an increase in levels is associated with prostate growth.(6) While PSA is primarily used as a screening tool for prostate cancer, it can also be used to determine prostate enlargement.

Clinical Trial Results

Avodart was investigated in three large, well-controlled, multi-center studies involving 4,325 men aged 50 and above with a serum PSA level greater than or equal to 1.5 ng/mL and less than 10 ng/mL, and BPH diagnosed by medical history and physician examination, including enlarged prostate (greater than or equal to 30 cc) and BPH symptoms that were moderate to severe according to the American Urological Association Symptom Index.

Data from these two-year clinical trials demonstrated that treatment with Avodart (0.5 mg once daily) reduced the risk of both AUR and BPH-related surgical intervention relative to placebo, improved BPH-related symptoms, decreased prostate volume, and increased maximum urinary flow rates.

"These data suggest that Avodart arrests the disease process of BPH in men with an enlarged prostate," said Gerald Andriole, MD, professor of surgery and chief of the Division of Urologic Surgery at the Washington University School of Medicine in St. Louis, Missouri, and an investigator in the study. "With Avodart, we have an important new treatment option for men with this disease."

Clinical trials of Avodart showed that it was generally well tolerated. Most side effects were mild or moderate and generally went away while on treatment in both the Avodart and placebo groups.

Drug-related side effects during the first six months were as follows: impotence (4.7 percent vs. 1.7 percent for placebo), decreased libido (3 percent vs. 1.4 percent), breast tenderness and breast enlargement (gynecomastia; 0.5 percent vs. 0.2 percent) and ejaculation disorders (1.4 percent vs. 0.5 percent). The incidence of most drug-related sexual side effects decreased with duration of treatment. The incidence of drug-related breast tenderness and breast enlargement remained constant over the treatment period. Ejaculate volume may be decreased in some patients with continued treatment. This decrease did not appear to interfere with normal sexual function.

Avodart should not be used in women and children. Women who are pregnant or may become pregnant should not handle Avodart because of possibility of absorption of Avodart and the subsequent potential risk to a male fetus.

Men treated with Avodart should not donate blood until at least six months after their final dose to prevent giving Avodart to a pregnant woman through a blood transfusion. Men with an allergic reaction to Avodart or its ingredients should not take it. Men with liver disease should talk to their doctor before taking Avodart.

Avodart will reduce the amount of PSA measured in the blood. A physician will be aware of this effect and can still use PSA to detect prostate cancer.

Although improvement in urinary symptoms was seen in some patients by three months, a therapeutic trial of at least six months is usually necessary to assess whether a beneficial response in symptom relief is achieved with Avodart.

Avodart, to be available for prescription in December 2002, was developed by GlaxoSmithKline, with U.S. operations in Philadelphia and Research Triangle Park, N.C., one of the world's leading research-based pharmaceutical and health care companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

For full prescribing information, please contact Veronica Grosshandler at 919-483-2839.

    References

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