GSK’s Avodart® / tamsulosin combination showed benefits for men with prostate enlargement

GlaxoSmithKline (GSK) announced today that it has filed a supplemental New Drug Application (sNDA) for Avodart® (dutasteride) with the US Food and Drug Administration (FDA) for prostate cancer risk reduction among men at increased risk of developing the disease. EU filings also are underway via the European Mutual Recognition Variation Procedure, with Sweden acting as the Reference Member State.

Issued:  Monday 12 October 2009, London, UK

GlaxoSmithKline (GSK) announced today that final results from a large, 4-year study showed that Avodart (dutasteride) and tamsulosin combination treatment reduced the risk of acute urinary retention (AUR) or Benign Prostatic Hyperplasia* (BPH)-related surgery and reduced the risk of BPH clinical progression more than tamsulosin alone**.  Combination treatment also delivered superior, sustained symptom improvement from month nine compared to either dutasteride or tamsulosin monotherapy.

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

The GSK-sponsored Combination therapy with Avodart and tamsulosin (CombAT) study, (just published online in European Urology)1,showed a significant 66 percent reduction in the risk of AUR or BPH-related surgery with combination treatment compared to tamsulosin (p < 0.001).  there was="" a="" 20 percent reduction compared="" to="" dutasteride (p="0.18)."  the="" risk of="" bph clinical progression with combination treatment="" was="" reduced by="" 44 percent compared="" to="" tamsulosin="" and="" 31 percent for="" those on="" dutasteride.  men in="" this study who had moderate-to-severe symptoms of="" bph at enrolment, reported a="" significant improvement="" in="" bph symptoms at 4 years, with a="" mean="" change="" from="" baseline of="" -6.3 points, compared="" to="" -3.8 for="" tamsulosin="" and="" -5.3 for="" dutasteride alone, as measured="" by="" the="" international prostate symptom score="">

The 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, with erectile dysfunction and retrograde ejaculation as the most commonly reported drug-related adverse events.  However, the incidence of heart failure observed was higher in the combination (0.9%) and tamsulosin arms (0.6%) than in the dutasteride group (0.2%).  There was no difference in overall cardiovascular events across treatment groups.  

Treating men with symptomatic enlarged prostate is important because if left untreated, in some men BPH can lead to AUR, a complete obstruction of urinary excretion, and BPH-related surgery.2Affecting nearly 50% of men over 50 years old,3,4 BPH is not life threatening, but its symptoms such as, hesitancy, interrupted weak urine flow, leaking or dribbling and more frequent urges and urination, may negatively affect patients suffering from BPH.

* BPH is also known as Enlarged Prostate (EP) in the US.

** 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.

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 outcome in men with moderate-to-severe symptomatic BPH.

•         The primary end-point at 4 years was time to first AUR event or BPH-related surgery.  Secondary end-points included clinical progression of BPH (defined as one of the following: symptom deterioration by IPSS =4 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 type 1 and type 2 forms of the enzyme 5-alpha reductase which converts testosterone into dihydrotestosterone (DHT), the primary male hormone 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.

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. 

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