Urinary incontinence (UI) is a common but often embarrassing and potentially socially debilitating condition affecting 200 million patients across the seven major markets*. UI is more likely to affect the female population, and is especially prevalent amongst the elderly. Although the prevalence of UI is high, in part because of the social stigma attached to the condition, treatment rates are traditionally low, with many patients receiving no pharmacological therapy at all.
Many patients will be self-diagnosed and those with milder symptoms will use pads and behavioural techniques, while some of the most severely affected patients will seek surgical intervention. No significant improvement has been made in the standard of UI drug treatment in 20 years, however, according to a new report by independent market analyst Datamonitor** an easy to use gel which avoids the side effects and pill burden associated with currently available drugs, will soon be on the market.
UI involves the involuntary leakage of urine, which can be leakage accompanied by or immediately preceded by urgency (urge UI), leakage on exertion (stress UI) or a combination of both (mixed UI). Although treatment rates are traditionally low due to a decreased awareness of the disease and a hesitance amongst patients to approach physicians, UI is a well-established condition and there have been drugs available to treat it for about two decades.
The current leading class of drugs are the anti-cholinergics, taken in a pill form. There are currently four once-a day anti-cholinergics on the market; Detrol (tolterodine), Ditropan (oxybutynin), Vesicare (solifenacin) and Enablex (darifenacin), with two more (Sanctura XR (trospium chloride) and Toviaz (fesoterodine)) set to come onto the market in the next couple of years.
There are, however, several unsatisfied needs in the UI market that the current anti-cholinergics do not satisfy. The current treatments demonstrate a high incidence of side effects associated with the cholinergic system, including the undesirable dry mouth. These cholinergic side effects play a significant role in worsening the patient's quality of life, according to Datamonitor central nervous system (CNS) analyst Henry Wheeler. “The current anti-cholinergics are not effective in all patients and sometimes the patient will have to trial several different anti-cholinergics before the optimal efficacy versus side effect profile is achieved,” he says.
The newer daily treatments offer the benefit of a reduced dosing regimen over the twice-dailies, and the variety of treatments currently available offer differing balances between efficacy and side effect profiles, with no significant breakthrough in the overall reduction in the side effects. However, due to there being a lack of other treatments currently available, this treatment class has remained the dominant class for the treatment of urge UI. There is however, a lack of available treatments for stress UI, with Europe having only the antidepressant Yentreve (duloxetine) on the market, and no treatment at all approved in the US. There is a need for alternative targets and mechanisms of action to deliver an improved efficacy profile.
Novel reformulations of the current anti-cholinergics have demonstrated some promise in the treatment of urge UI in reducing the anti-cholinergic side effects. A topical patch, Oxytrol, containing a traditional anti-cholinergic drug, oxybutynin, produced by Watson was thought to be able to revolutionize the UI market, bypassing the gastro-intestinal (GI) tract and thus the cholinergically observed side effects, Wheeler says. “Unfortunately due to side effects experienced with the patch itself, such as skin irritation and the fact that the patch was not potent enough – in some cases requiring the user to wear several patches – the patch never really took off.”
In a promising move for UI sufferers, Watson and Antares are currently developing a topical gel formulation of oxybutynin that will have all the benefits of the anti-cholinergic treatments without the unwanted anti-cholinergic side effects. Watson has announced positive Phase III data from its oxybutynin gel and is expected to launch its gel in early 2009. Meanwhile, Antares' oxybutynin gel is currently in Phase III trials. With a fast track program, Antares expect to have its product on the market six months after Watson's, Wheeler says. “The gel will come as a welcome relief to many patients experiencing the anti-cholinergic side effects, in particular elderly patients who already have to deal with a high pill burden.
“The gel treatment is forecast to prosper by offering patients an alternative to the current oral treatments, and thus succeeding in a niche market. Datamonitor forecasts sales will reach over $200m,” he says.
It is worth noting that while drug delivery reformulations offer a mid-term opportunity in the UI market, for a truly commercially successful long-term approach, and for a significantly improved benefit to the patient, a novel mechanism of therapeutic action is required, Wheeler says. “This would benefit patients not responding to the current anti-cholinergics, or those that experience too many unwanted side effects with the current drugs. Examples of the possible mechanisms of action beyond the anti-cholinergics can be observed in the development pipeline, which include the NK-1 antagonists and the adrenergic modulators.”
There is still a great-unsatisfied need in the stress UI market. While drugs are available to treat urge UI, there are no licensed treatments in the US and only the antidepressant, Yentreve (duloxetine) in Europe to treat stress UI.
The untapped stress urinary incontinence (SUI) market in the US is an area of great unsatisfied medical need, with a potential 28 million SUI patients in the US alone, Wheeler says. “A drug that is FDA approved for SUI would be a welcome relief to many SUI sufferers and would benefit from first to market status in the US,” he says.
Currently SUI is treated with the use of pads or surgical intervention. There is, as such, great potential for a pharmaceutical company to move into this market and market a drug for SUI in the US. The promising mechanisms of action in the current SUI pipeline include drugs that act on the adrenergic and NK-1 mechanisms.
“Several treatments in early Phase II are currently being developed for the potential treatment of SUI and Datamonitor believe current players would be well served to invest in this niche patient group,” Wheeler says.
* The seven major pharmaceutical markets are the US, UK, France, Germany, Italy, Spain and Japan.
** Pipeline and Commercial Insight: Urinary Incontinence - Lifecycle management strategies retain mid-term market growth