GlaxoSmithKline plc (GSK) today announces that it has received European approvals, for Avodart® (dutasteride), a new treatment for benign prostatic hyperplasia (BPH). Major European countries have approved an indication for the use of Avodart® in the treatment of moderate to severe symptoms of BPH and for the reduction in risk of acute urinary retention (AUR) and surgery, in patients with BPH. Following review under the Mutual Recognition Procedure (MRP), these approvals come 90 days after dutasteride was first approved by the Reference Member State Sweden; (in Sweden dutasteride has been approved with the trade name Avolve®). GSK plan to market Avodart® in all major European markets with launches in the first half of 2003.

Commenting on the approval, Professor Roger Kirby, Professor of Urology, St George's Hospital, London said: "Avodart provides BPH patients and their doctors with a new long-term treatment option. In clinical trials involving in excess of 4,300 patients with BPH over two years, Avodart provided long lasting symptom improvement and reduced the risk of AUR - the sudden complete inability to urinate - by 57 percent, and the need for BPH-related surgery by 48 percent."

Avodart is the first and only 5-alpha reductase inhibitor (5ARI) that inhibits both the type 1 and 2 isoenzymes of 5-alpha reductase, the enzyme responsible for converting testosterone to dihydrotestosterone (DHT) in the prostate and other tissues. DHT is the primary cause of prostate growth that has been proven to play a key role in the development and progression of BPH. Avodart decreases levels of DHT by 90 percent and this is maintained at two years.

BPH is a common benign growth in ageing men. It is this non-cancerous enlargement of the prostate gland that frequently causes lower urinary tract symptoms (LUTS). BPH is a progressive disease and if left untreated for a long duration, can in severe cases result in complications such as AUR and surgery requiring hospitalisation.

Overall, in clinical trials, the most commonly reported adverse events as reported in the approved Summary of Product Characteristics were impotence (6%), altered / decreased libido (3.7%), ejaculation disorder (1.8%), gynaecomastia (1.3%).

Avodart was developed by GlaxoSmithKline, 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.

Notes to the Editor:

An original NDA, with one-year data for dutasteride in the treatment of symptomatic BPH, was approved by the FDA in November 2001. A supplemental NDA (sNDA) with two-year treatment data for dutasteride was approved by the FDA in October 2002. Based upon this sNDA approval, dutasteride in the US is indicated for the treatment of symptomatic BPH in men with an enlarged prostate to improve symptoms, reduce the risk of AUR and reduce the risk of the need for BPH-related surgery. Dutasteride will be launched in the US, and in major European markets under the trade name Avodart, throughout 2002/2003.

Background on BPH

• Current worldwide sales of treatments for BPH are £1,658 million.¹
• BPH is one of the most common health problems in older men.2 BPH often begins after age 50 and progresses as men age. More than half of men over age 60 have BPH,3 and by age 80, nearly 80 percent.^3,4 It is estimated that over 20 million European men suffer from BPH.
• 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. 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 an enzyme called "prostate-specific antigen," or PSA. PSA is produced by the prostate, and an increase in levels could be 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

• Dutasteride was investigated in three large, well-controlled multi-center studies involving 4,325 men aged 50 and above with a serum PSA level ³ 1.5 ng/mL and < 10 ng/mL, and BPH diagnosed by medical history and physical 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 dutasteride (0.5 mg once daily) reduced the risk of both AUR and the need for BPH-related surgical intervention relative to placebo, improved BPH-related symptoms, decreased prostate volume, and increased maximum urinary flow rates.
• Most side effects were mild or moderate and generally went away while on treatment in both the dutasteride 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).
• 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 improvement is achieved with dutasteride.

References
¹ Global Business & Commercial Analysis Database, GSK .
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 follow-up study. J Urol 1999; 162:376-382.
³ American Foundation for Urologic Disease (AFUD). What is the Prostate and What Does it Do? http://www.afud.org.
⁴ Marcelli M, Cunningham, GR. Hormonal signaling in prostatic hyperplasia and neuroplasia. J Clin Endocrin Metab 1999; 84(10):3463-3468.
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 Anderson JB, Roehrborn CG, Schalken JA, Emberton M. The progression of benign prostatic hyperplasia: examining the evidence and determining the risk. Eur Urol 2001; 39: 390-399.
⁷ Girman CJ, Epstein RS, Jacobsen SJ, Guess HA, Panser LA, Oesterling JE, Lieber MM. Natural history of prostatism: impact of urinary symptoms on quality of life in 2115 randomly selected community men. Urol 1994; 44:825-831.
⁸ Jacobsen SJ, Jacobsen DJ, Girman CJ et al. Natural history of prostatism: risk factors for acute urinary retention. J Urol 1997; 158: 481-487.
⁹ 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.

About GSK:
GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, GlaxoSmithKline cautions investors that any forward-looking statements or projections made by GSK, including those made in this news release, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the company's operations are discussed in the section "Cautionary factors that may affect future results" in GSK's results announcement for the year ended 31 December 2001, filed with the U.S. Securities and Exchange Commission."

Updated December 9, 2002 - © 2001-2005 GlaxoSmithKline - All Rights Reserved Legal Notices - Privacy Statement - Accessibility