Vesicare (solifenacin succinate) is an oral selective muscarinic receptor antagonist developed by Yamanouchi, Japan’s third largest pharmaceutical company. In April 2005, Yamanouchi merged with Fujisawa to form Astellas Pharma. Vesicare is indicated for the treatment of urinary frequency, urgency and incontinence associated with overactive bladder.
Vesicare is now marketed in Europe and the US, having secured regulatory approval from the European Medicines Agency and US Food and Drug Administration in June and November 2004 respectively. In Japan regulatory filing was completed in 2005. In April 2006, Astellas obtained approval for Vesicare in Japan.
Vesicare OD, an orally disintegrated version of Vesicare, was approved in Japan in October 2010. Vesicare OD was launched in the Japanese market in April 2011.
Selective anticholinergic drugs may offer improved treatment of overactive bladder
Overactive bladder 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 and muscarinic receptors in smooth muscle form an important part of the medical treatment of overactive bladder. 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 overactive bladder with a lower potential for systemic adverse events.
Clinical trials support efficacy in overactive bladder
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 marks Astellas’s entry into the US pharmaceutical market
Vesicare is the first product to be launched by Astellas Pharma US (formerly Yamanouchi Pharma America), the company’s independent sales and marketing network in the US. Formed in October 2001, it is designed to spearhead Astellas’s entry into the US pharmaceutical market, where it will focus initially on the company’s urology products.
In August 2003 the company entered into an agreement with GlaxoSmithKline to co-promote Vesicare in the US market, a strategy designed to accelerate the drug’s market entry.
Astellas Pharma US has been a major force in the urology market with tamulosin, a selective alpha1-blocker that improves the functional symptoms of benign prostatic hyperplasia and reportedly the leading treatment worldwide for this condition. Boehringer Ingelheim markets tamulosin as Flomax in the US. The US urology sector is 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 overactive bladder, only 20% receive treatment. Improved treatments have seen the market expand to around $1bn a year, which has scope to increase further as new treatments are approved.