Avodart (dutasteride) in combination with tamsulosin shows benefits for men with benign prostatic hyperplasia (enlarged prostate)

LONDON, Oct. 12, 2009--GlaxoSmithKline (GSK) announced today the final results from its 4-year CombAT (Combination therapy with Avodart and Tamsulosin) study, which have been published online in European Urology. The results show that combined treatment with Avodart and tamsulosin significantly reduces the risk of acute urinary retention (AUR) or BPH-related surgery by 66% compared with tamsulosin* alone (p<0.001). It was also shown that combination therapy significantly reduces the risk of BPH disease progression by 44% compared with tamsulosin and 31% compared with dutasteride alone1.

BPH affects nearly 50% of men over 50 years old worldwide.2,3 It is not a life threatening condition but associated symptoms, such as incontinence and the urge to urinate more frequently, can impair the quality of life of men suffering from BPH and their families.4 If left untreated, symptomatic enlarged prostate can increase the risk of serious long-term complications such as AUR, hospitalisation and surgery.5

“BPH is a progressive disease causing discomfort, inconvenience and embarrassment for many men. CombAT provides evidence that combination therapy may benefit these men, potentially reducing the long-term risk of disease progression and improving their symptoms.” said Dr Claus G. Roehrborn, principle investigator and lead author of the CombAT study publication.

Dr Pim Kon, Medical Director, GlaxoSmithKline, commented, “There is still a huge unmet need in the treatment of BPH. In the UK there are 3.2 million men over 50 years old with BPH. Of those, only 1.5 million have a diagnosis with just 450,000 men currently receiving medical treatment. The high prevalence of this progressive disease and the detrimental effect it has on the quality of life of patients highlights the need for effective treatment options. Enabling GPs to offer better treatment potentially reduces the development of complications such as acute urinary retention and the need for prostate surgery. ”

Men in this study all had moderate-to-severe symptoms of BPH at enrolment. Those treated with combination therapy reported a significant improvement in BPH symptoms at 4 years, as measured by the International Prostate Symptom Score (IPSS), with a mean change from baseline of -6.3 points, compared to -3.8 for tamsulosin and -5.3 for dutasteride alone**.

“As a treating clinician, the CombAT study results are very encouraging as they show that BPH can be effectively treated using combination therapy, reducing the risk of disease progression and surgery related to this disease. Disease progression often leads to more severe symptoms and can cause AUR, a sudden inability to pass urine, which is always painful and involves treatment with catherisation or prostate surgery. This may have a serious impact on a patient’s quality of life, as can the fear that AUR may recur”, said Dr Mark Emberton, Urology Consultant, University College of London.

Combination therapy was generally well-tolerated and most reported drug-related adverse events were as anticipated from the known safety profiles of the two drugs. Although there were no significant differences between combination therapy and the two monotherapies in terms of overall withdrawal rates due to drug-related adverse events, the incidence of events in the combination group was greater, with erectile dysfunction and difficulty with ejaculation being the most commonly reported adverse events. The incidence of heart failure was observed to be higher in the combination (0.9%) and tamsulosin (0.6%) arms than in the dutasteride group (0.2%) although the overall incidence after 4 years of treatment in the CombAT study was less than 1%. No causal link between heart failure and dutasteride, either alone or in combination with tamsulosin, has been established. There was no difference in the overall incidence of cardiovascular events across all treatment groups.

-ENDS-

 

* Tamsulosin is not indicated to reduce the risk of AUR or BPH-related surgery.

** IPSS is a validated 7-item self-reported questionnaire designed to quantify urinary symptoms.

 

Note to editors:

About CombAT

CombAT was a 4-year multinational randomised study of 4,844 men at increased risk of BPH progression, investigating whether combination treatment with the 5-alpha reductase inhibitor (5ARI), dutasteride (0.5mg), and an alpha blocker, tamsulosin (0.4mg), was more effective than either monotherapy in improving symptoms and clinical outcomes in men with moderate to severe symptomatic benign prostatic hyperplasia.

The primary end-point at 4 years was time to first AUR event or BPH-related surgery vs either monotherapy. Secondary end-points included clinical progression of BPH (defined as one of the following: symptom deterioration by IPSS ?? points on two consecutive visits; BPH-related AUR; BPH-related urinary incontinence; recurrent BPH-related urinary tract infections (UTI) or urosepsis; BPH-related renal insufficiency), symptom improvement, urinary flow rate improvements, prostate volume and serum prostate specific antigen (PSA) changes.

About dutasteride

Dutasteride is a dual inhibitor of both the type 1 and type 2 forms of the enzyme 5-alpha reductase which converts testosterone into dihydrotestosterone (DHT), the male hormone primarily responsible for prostate growth and BPH development.6 Dutasteride monotherapy is indicated for the treatment of moderate-to-severe symptoms of BPH, and to reduce the risk of AUR and prostate surgery in men with BPH.7

Women and children should not take dutasteride. Women who are or could become pregnant should not handle dutasteride due to the potential risk of a specific birth defect. Blood should not be donated until at least 6 months following the last dose of dutasteride. Possible side effects include sexually related side effects and swelling or tenderness of the breast. Other urological diseases, including prostate cancer, should be ruled out prior to treatment with dutasteride.

About BPH

BPH is the term used to describe the benign – ie. non-cancerous – enlargement of the prostate gland; a walnut-shaped gland located beneath the bladder. In BPH, the benign enlargement of the prostate causes a narrowing of the urethra where it passes through the prostate, leading in turn to bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS). Common LUTS symptoms include difficulty urinating, incontinence and the urge to urinate more frequently.8

References

1. Roehrborn CG, et al. The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study, Eur Urol (2009), doi:10.1016/j.eururo.2009.09.035

2. Napalkov P, Maisonneuve P, Boyle P. Worldwide patterns of prevalence and mortality from benign prostatic hyperplasia. Urology 1995; 46: 41-46

3. McVary KT. BPH: Epidemiology and Comorbidities. Am J of Managed Care 2006; 12 (5): 122-128

4. Levy A, Samraj GP. Benign prostatic hyperplasia: when to 'watch and wait,' when and how to treat. Cleve Clin J Med. 2007;74 Suppl 3:S15-20

5. Marberger M, Harkawayb R and de la Rosette J. Optimising the Medical Management of Benign Prostatic Hyperplasia. European Urology 45 (2004) 411?

6. Clark RV, Hermann DJ, Cunningham GR, Wilson TH, Morrill BB, Hobbs S. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab 2004; 89: 2179-2184

7. GSK. Avodart Summary of Product Characteristics. GSK UK, Uxbridge, Middlesex; 2008. http://emc.medicines.org.uk/medicine/11618

8. National Institute for Health and Clinical Excellence (NICE) Scope. Male lower urinary tract symptoms (LUTS/BPH) draft scope for consultation. 4th September-1st October 2007

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.

Cautionary statement regarding forward-looking statements Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company' s Annual Report on Form 20-F for 2007.

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Posted: October 2009

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