Vesicare - Oral Selective Muscarinic Receptor Antagonist for Overactive Bladder (OAB)

Vesicare (solifenacin succinate) is an oral selective muscarinic receptor antagonist developed by Yamanouchi, Japan's third largest pharmaceutical company. It is indicated for the treatment of urinary frequency, urgency and incontinence associated with OAB.

Vesicare is now marketed in both Europe and the US, having secured regulatory approval from the EMEA and FDA in June and November 2004 respectively. It is also in phase III clinical trials in Japan, where regulatory filing is anticipated in 2005.

SELECTIVE ANTICHOLINERGIC DRUGS MAY OFFER IMPROVED TREATMENT OF OAB

OAB is a condition in which the detrusor muscle, which surrounds the bladder and, in conjunction with the urethral sphincter controls micturition, contracts spastically causing sustained, high pressure in the bladder and a subsequent urgent need to urinate (so-called urgency). Estimated to affect 17-20 million people in the US alone, it is a distressing condition that can diminish people's self-esteem and quality of life. Malfunction of the detrusor muscle can arise from a number of causes including:

• Nerve damage from abdominal or pelvic trauma, or surgery
• Bladder stones
• Side effects of drug therapy
• Neurological diseases such as multiple sclerosis, Parkinson's disease, stroke or spinal cord lesions

Anticholinergic drugs that act on central nervous system (CNS) and muscarinic receptors in smooth muscle form an important part of the medical treatment of OAB. By relaxing the smooth muscle of the bladder they reduce detrusor contraction and subsequent wetting accidents.

Conventional anticholinergic drugs have a number of unpleasant side effects, such as dry mouth, blurred vision and constipation. This has led to the search for more selective anticholinergic drugs that provide bladder-specific cholinergic blockade. Yamanouchi's investigational muscarinic antagonist solifenacin succinate is thought to act primarily on muscarinic receptors in the smooth muscle of the bladder. As such it should control symptoms of OAB with a lower potential for systemic adverse events.

CLINICAL TRIALS SUPPORT EFFICACY IN OAB

The efficacy and safety of solifenacin succinate has been investigated in a series of clinical trials, the most recent of which were two US randomised, double-blind, placebo-controlled, parallel-group, fixed-dose, multicentre studies. Data from these trials was presented at the 2003 American Urological Association Meeting held in Chicago. Involving 1,208 patients, the studies showed solifenacin was significantly superior to placebo in decreasing the number of voids per day (-2.7 vs -1.4; p<0.001), decreasing incontinence episodes per day (-2.0 vs -1.2; p<0.001) and increasing the volume voided (+46.8ml vs +7.7ml; p< 0.001). Additionally, 53% of patients were completely dry by study end compared with only 31.4% of those on placebo (P<0.001).

A European trial in 857 patients produced similar results, with significant differences again reported for solifenacin over placebo with respect to decreases in voids per day, urge episodes and urinary urge incontinence as well as increases in bladder volume. Active treatment was well tolerated, although not completely devoid of adverse effects. Dry mouth and constipation occurred with greater frequency in the active treatment arm compared with placebo.

SOLIFENACIN SHOULD MARK YPA'S ENTRY INTO THE US PHARMACEUTICAL MARKET

Vesicare® will be the first product to be launched by Yamanouchi Pharma America (YPA), the company's new independent sales and marketing network in the US. Formed in October 2001, it is designed to spearhead Yamanouchi's entry into the world's largest pharmaceutical market, where it will focus initially on the company's urology products.

In August 2003 Yamanouchi entered into an agreement with GlaxoSmithKline (GSK) under which GSK and YPA will co-promote Vesicare® in the US market, a strategy designed to accelerate the drug's market entry. For GSK, the agreement helps strengthen its late-stage product development pipeline.

MARKETING COMMENTARY

Yamanouchi is already a major force in the urology market with tamulosin, a selective alpha1-blocker that improves the functional symptoms of benign prostatic hyperplasia (BHP) and reportedly the leading treatment worldwide for this condition. Boehringer Ingelheim markets tamulosin as Flomax® in the United States. The recent launch of Vesicare will strengthen the company's position in the US urology sector, projected to grow significantly on the back of an ageing population and current low treatment rates. Of the 20 million Americans who experience symptoms associated with OAB, currently only 20% receive treatment. Improved treatments have seen the market expand to around $1 billion a year, which has scope to increase further as new treatments are approved.