BBI Contributing Editor

ORLANDO, Florida — Several new bulking agent materials for the treatment of stress urinary incontinence were discussed at the centennial celebration and annual meeting of the American Urological Association (AUA; Baltimore, Maryland), held here in late May. Prior to 1995, when C.R. Bard (Murray Hill, New Jersey) introduced Contigen, there were no options for the 11 million women with stress incontinence — an involuntary leakage of urine — other than surgery. Contigen, a collagen-based bulking agent that adds volume to the urethral sphincter for tighter closure, provides women with an office-based, nonsurgical alternative to treat intrinsic sphincter deficiency (ISD), a form of stress incontinence.

Initially, bulking agents such as Contigen were intended to treat the 2 million patients that specifically had intrinsic sphincter deficiency, where total closure of the sphincter is not achieved. The remaining 9 million stress incontinent patients' condition was thought to be due to urethral hypermobility, where the urethra moves or tugs on the sphincter when abdominal pressure is applied, allowing urine to leak. Until now, bulking the sphincter has not been indicated for treatment of hypermobility, but thought leaders today suggest that mild to moderate stress incontinence is not necessarily due to one or the other condition.

According to Alan Wein, MD, professor and chairman of the University of Pennsylvania School of Medicine (Philadelphia, Pennsylvania), who led a plenary session titled "Past, Present and Future Perspectives of Surgery to Correct Urinary Incontinence in Women," "one rarely sees hypermobility without ISD; they are not two separate entities, and hypermobility is not the cause for the incontinence." He added that achieving coaptation at the urethral outlet at rest should improve these patients' symptoms.

This theory also was supported by Rodney Appell, MD, of Baylor College of Medicine (Houston, Texas) in his paper, "Urethral Hypermobility and Intrinsic Sphincteric Deficiency — Separate Entities or Coexisting Factors in Women with Stress Urinary Incontinence?" He concluded that urethral hypermobility and intrinsic sphincter deficiency "are co-factors and not separate entities in the pathogenesis of stress urinary incontinence." He added that "further studies may shed more light on the true efficacy of various treatment modalities." What this new thinking could mean to manufacturers of stress incontinence products is that the entire population of 11 million women in the U.S. — and not just a portion of this population — may be a candidate for products that are designed to address mild to moderate stress incontinence.

This is better news for the ISD companies producing bulking agents once thought only to be used for the 2 million ISD patients. Somewhat in response to this newer thinking, but mostly in response to the unsatisfied market for bulking agents, there is a flurry of fresh activity in bulking agents. The fact that so many new companies are entering this market testifies to the fact that the opportunity is large. Industry experts predict that with a product that is biocompatible, does not migrate, is easy to use and is durable, the market should easily reach $200 million annually in the U.S.

U.S. annual sales for bulking agents have remained steady at about $50 million a year in recent years, while the market potential could be well over $200 million if only 10% of the ISD patients were treated. In addition, there are 9 million patients with SUI due to hypermobility (if one were to separate the two conditions), and only 200,000 surgeries for incontinence, leaving more than 8 million untreated patients who may also be candidates for bulking agents.

There are many reasons why patients are not seeking treatment, including:

• They don't realize that incontinence is a medical problem and can be treated.
• Primary care physicians don't ask their patients if they have incontinence because they are unaware of non-surgical alternatives.
• Patients do not want surgery, and are unaware of other options.

One big reason why clinicians are not promoting injection therapy as a non-surgical option is that the two bulking agents currently available in the U.S. do not meet critical requirements for success. According to a presentation at AUA by R. Dmochowski, MD; M. Techetgen, MD; and D. Staskin, MD, those include: 1) Being non-immunogenic, hypoallergenic and non-antigenic; 2) Being biocompatible; not creating inflammatory response; 3) Having satisfactory wound healing with minimal fibrotic ingrowth; 4) retaining bulking effect over prolonged periods of time; 5) Having particle sizes above 110 microns or that instigate adhesion to host tissue; and 6) Carrier and bulking materials do not separate upon injection.

This is what has attracted so many new entrants into this field — a large untapped market coupled with unmet market demands (see Table 5). The hope is that at least one of the new entrants may meet the market demands for a better bulking agent and begin to help the millions of American women seeking a higher quality of life.