FDA approves Avodart, the first dual-acting 5 alpha-reductase inhibitor for benign prostatic hyperplasia (BPH)

Avodart Improves Symptoms and Reduces Risk of Acute Urinary Retention and the Need for BPH-Related Surgery in Men with an Enlarged Prostate

London, October 10, 2002 - The U.S. Food and Drug Administration (FDA) today approved a supplemental new drug application for Avodart® (dutasteride), manufactured by GlaxoSmithKline (GSK), for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate. This new medicine for these patients will improve urinary symptoms, reduce risk of acute urinary retention (AUR) and reduce the risk of the need for BPH-related surgery.

Dutasteride, 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. Dutasteride's dual inhibition decreases levels of DHT by 90 percent at two weeks and 93 percent at two years.

By reducing DHT levels, dutasteride reduces the size of an enlarged prostate. 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. Dutasteride 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 dutasteride, 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 dutasteride, 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."

Dutasteride was approved by the Swedish regulatory authority (MPA) on July 24th 2002. It will be marketed in Sweden by the trade name AvolveÒ. The MPA agreed to act as the Reference Member State for the Mutual Recognition procedure within Europe and GSK plan to market the drug in all major European markets once approvals are finalised during 2003. The European trade name (Avolve) is to be confirmed.

NOTES TO EDITORS

Background on BPH

• 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 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

• 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 BPH-related surgical intervention relative to placebo, improved BPH-related symptoms, decreased prostate volume, and increased maximum urinary flow rates.

   

• Dutasteride should not be used in women and children. Women who are pregnant or may become pregnant should not handle dutasteride because of possibility of absorption of dutasteride and subsequent potential risk to a male foetus.

   

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

   

• Clinical trials of dutasteride showed that it was generally well tolerated. 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).

   

• The incidence of most drug-related sexual adverse events 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.

   

• Dutasteride 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 dutasteride.

Dutasteride 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.

References

¹ Roehrborn CG, Nickel C, Hoefner K, Andriole G. Efficacy and safety of a dual inhibitor of 5 alpha reductase type 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urol. 2002;60:434-441

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.