Avodart

Business Editors

RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--Jan. 14, 2003

Avodart Arrests Disease Process and Provides Long-Term Approach for

Treating BPH

GlaxoSmithKline's new medicine, Avodart(TM)(dutasteride 0.5 mg) for symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate is now available for prescription in the U.S.

Avodart, a 5 alpha-reductase inhibitor (5 A-RI), arrests the BPH disease process - unlike the most commonly prescribed BPH treatment, alpha-blockers, which are indicated only for symptom improvement. Avodart inhibits dihydrotestosterone (DHT), the primary cause of prostate growth, and shrinks the prostate. Avodart also improves urinary symptoms; and reduces the risk of acute urinary retention (AUR, the sudden inability to urinate) and the risk of the need for BPH-related surgery.

"Currently, 85 percent of men who receive a prescription treatment for BPH are treated with alpha-blockers," said Stan Hull, senior vice president, U.S. Pharmaceuticals, GlaxoSmithKline. "We believe men with symptomatic BPH who are at risk for disease progression should be aware of and have access to medicines that not only treat BPH symptoms, but also arrest the disease process that can lead to long-term complications."

Symptomatic BPH does not progress in all patients. PSA (prostate-specific antigen) levels in the blood can be used as a marker for predicting which patients are at increased risk for BPH disease progression.(1) Patients with symptomatic BPH, a PSA greater than 1.5 ng/mL and an enlarged prostate are at greater risk for further prostate enlargement that can lead to complications. Patients in this group with a prostate volume greater than or equal to 30 cc may benefit from Avodart, a new treatment that addresses prostate growth, the underlying cause of BPH.

Patients with a PSA less than 1.5 ng/mL and lower urinary tract symptoms are at lower risk for future complications. These patients may only require a treatment plan that alleviates their symptoms.

Avodart Mechanism of Action

Avodart is the first and only medicine that inhibits both the type 1 and type 2 enzymes responsible for the conversion of testosterone into dihydrotestosterone (DHT) in the prostate and other tissues. DHT is the primary cause of prostate growth and plays a key role in the development and progression of BPH. Avodart decreases levels of DHT by 90 percent after two weeks and by 93 percent after long-term therapy (at two years).

By reducing DHT levels, Avodart reduces the size of an enlarged prostate. In clinical studies, this reduction in prostate volume began as early as one month and continued through the treatment period. Shrinking the enlarged prostate relieves urinary obstruction and improves urinary flow.

"Urologists and primary care physicians now have an important new treatment option for men who are at greater risk for prostate enlargement that leads to progression of the disease," 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. "With Avodart, we can take a long-term approach to treating men's BPH and reduce their risk of AUR and BPH-related surgery."

About BPH

BPH, one of the most common health problems in older men,(2) is a progressive disease in which the prostate gland surrounding the urethra enlarges.(3) As it grows, the prostate obstructs the urethra, the tube through which urine flows, causing urinary difficulties. BPH symptoms may interfere with a man's daily activities and reduce the sense of well-being.(4)

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.(3) A 60-year-old man with a 20-year life expectancy has a 23 percent risk of developing acute urinary retention.(6) Lifetime risk is increased in men with symptomatic BPH and an enlarged prostate.(7) Among men 60 years or older with prostatic enlargement and obstructive symptoms, the 20-year probability of needing BPH-related surgery is 39 percent.(7)

BPH often begins after age 50 and can progress and worsen as men age. More than half of men over age 60 experience BPH,(8) and by age 80, nearly 80 percent of men have the disease.(8,9) In the United States alone, 375,000 hospital stays each year involve a diagnosis of BPH.(5)

The American Urological Association (AUA) recommends that men with at least a 10-year life expectancy have a yearly prostate checkup beginning at age 50. This checkup may include a discussion of symptoms, a digital rectal exam and a prostate-specific antigen (PSA) test. African-American men or those with a family history of prostate cancer should begin these tests at age 45. An immediate checkup should be performed on any man who suddenly develops persistent urinary problems.

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.

Clinical trials of Avodart showed that it was generally well-tolerated. Overall, 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 over the course of the study. 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 directly because of the possibility of absorption of Avodart and the subsequent potential risk to a male fetus.

Lower urinary tract symptoms of BPH can be indicative of other urological diseases, including prostate cancer. Patients should be assessed to rule out other urological diseases prior to treatment with Avodart. Patients with a large residual urinary volume and/or severely diminished urinary flow may not be good candidates for 5 alpha-reductase inhibitor therapy and should be carefully monitored for obstructive uropathy.

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, but it does this in a predictable manner. A physician will be aware of this effect and can still use the PSA test to screen patients for prostate cancer.

While some men have fewer problems and symptoms after three months of treatment with Avodart, a treatment period of at least six months is usually necessary to see if Avodart will improve symptoms.

Avodart received approval by the U.S. Food and Drug Administration (FDA) in October 2002, as well as European Marketing Authorization from the European Agency for the Evaluation of Medicinal Products (EMEA) in December 2002.

Avodart 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:

(1) Roehrborn CG, McConnell JD, Lieber M, et al. Serum

prostate-specific antigen concentration is a powerful

predictor of acute urinary retention and need for surgery in

men with clinical benign prostatic hyperplasia. Urology. 1999;

53(3): 473-480.

(2) Meigs JB, Barry MJ, Giovannucci E, Rimm EB, Stampfer MJ,

Kawachi I. Incidence rates and risk factors for acute urinary

retention: the health professionals followup study. J Urol

1999; 162:376-382.

(3) Anderson JB, Roehrborn GH, Schalkon JA, Emberton M. The

progression of benign prostatic hyperplasia: examining the

evidence and determining the risk. Eur Urol. 2001;39: 390-399.

(4) Girman CJ, Epstein RS, Jacobsen SJ, et al. Natural history of

prostatism: impact of urinary symptoms on quality of life in

2115 randomly selected community men. Urol 1994; 44:825-831.

(5) National Institute for Diabetes and Digestive and Kidney

Diseases (NIDDK). Prostate Enlargement: Benign Prostatic

Hyperplasia. June 2002.

http://www.niddk.nih.gov/health/urology/pubs/prostate/index.htm.

(6) Jacobsen SJ, Jacobsen DJ, Girman CJ, et al. Natural history of

prostatism: risk factors for acute urinary retention. J Urol

1997; 158:481-487.

(7) Arrighi HM, Metter EJ, Guess HA, Fozzard JL. Natural history

of benign prostatic hyperplasia and risk of prostatectomy: The

Baltimore Longitudinal Study of Aging. Urol (supplement) 1991;

38(1):4-8.

(8) American Foundation for Urologic Disease (AFUD). What is the

Prostate and What Does it Do? http://www.afud.org.

(9) Marcelli M, Cunningham, GR. Hormonal signaling in prostatic

hyperplasia and neuroplasia. J Clin Endocrin Metab 1999; 84

(10):3463-3468.

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