Market Opportunity for Treatment of PBS
Presently, no approved products exist for treating painful bladder syndrome and those that have been approved for interstitial cystitis, a subset of PBS, are based on clinical studies which have shown the drugs to be marginally effective. Consequently, there remains a significant need for new therapeutic interventions such as URG101 that can address the underlying disease process while also providing acute symptom relief. PBS is a chronic disease characterized by moderate to severe pelvic pain, urgency, urinary frequency, dyspareunia (painful intercourse) with symptoms originating from the bladder. Current epidemiology data shows that PBS may be much more prevalent than previously thought.
One theory of PBSís pathological cause implicates a dysfunction of the bladder epithelium surface called the urothelium. The epithelium is the inner lining of tissue organs. Normally, the urothelium is covered with a mucus layer, the glycosaminoglycan (GAG) layer, which is thought to protect the bladder from urinary toxins. A deficiency in the GAG layer would allow these toxins to penetrate into the bladder wall activating pain sensing nerves and causing bladder muscle spasms. These spasms trigger responses to urinate resulting in the symptoms of pelvic pain, urgency and frequency, the constellation of symptoms associated with this disease. Once established, PBS can be a chronic disease, which can persist throughout life and can have a devastating impact on quality of life.
Urigen believes that the prevalence of PBS in North America is estimated to be 10.5 million, of which 3.8 million would experience severe enough symptoms to be classified as having interstitial cystitis, a subset of PBS. This estimate was based on studies conducted by Clemens and Collegues from Northwestern University and Matt T. Rosenberg and Matthew Hazzard at the Mid-Michigan Health Centers. Each group independently concluded that the number of subjects with interstitial cystitis have been significantly underestimated. Drs Rosenberg and Hazzard evaluated over 1,000 female primary care patients over the course of a year using a pain, urgency/frequency questionnaire to categorize subjects as symptomatic or not. Urigen calculated its PBS estimate(s) based on a cutoff score of 10 on the pain, urgency/frequency scale, assuming a 50% rate for men relative to women, and for IC a more stringent cutoff score of 15.
Clinical Trial Status
Urigen filed an IND in 2005 to initiate a Phase IIb multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of intravesical alkalinized lidocaine-heparin for the symptoms of pelvic pain and urgency of bladder origin. A Phase I study was not required because the components of URG101 are FDA-approved for other uses. The study enrolled 90 subjects randomized to drug vs. placebo in a 1:1 ratio. The study included a clinically relevant three-week treatment phase to evaluate the safety and efficacy of URG101 for the treatment of pelvic pain and/or urgency of bladder origin. While URG101 did not meet the primary endpoint in the study, the trial provided information necessary to proceed with development of the product. According to press releases issued by Acorda Therapeutics, Inc. in 2004 and 2006, there are other examples of clinical trials not achieving primary endpoints, but there are lessons learned in the study that can lead to success in Phase III trials. The rationale for continued development of URG101 was several-fold: the largest and most experienced clinical trial site met both the primary (70% drug response versus 17% placebo) and secondary endpoints of the study. Additionally, the study achieved a high level of statistical significance on improvement in urgency with just one dose over placebo and trended toward improvement in pain with just one dose. These results indicated that, in a controlled clinical trial, subjects receiving study drug experienced meaningful symptom improvement in both urgency and bladder pain over placebo.
In a subsequent Phase II multi-center, double-blind, randomized, placebo-controlled, cross-over study comparing URG101 to placebo an interim analysis of 21 completed patients demonstrated that URG101 primary and secondary efficacy measurements in the study were significantly better than placebo. Top line data analysis findings included:
- Primary Endpoint - Improvement in Average Daytime Pain (p=0.03).
- Secondary Endpoints - Improvement in Daytime Urgency (p=0.03) and Total Symptom Score (p=0.03). In addition, patients reported improved symptom relief with URG101 as measured by PORIS (p=0.01).
Interview with C. Lowell Parsons, MD, Scientific Founder at Urigen
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"The employment of instillation therapy for interstitial cystitis / bladder pain syndrome is really evolving. And key part is that you can deliver it to the bladder with a catheter, large doses of medication that can be quite effective at controlling the symptoms and the disease Ė more so than you can if you give an oral medication.
There are a couple of downsides. Obviously, you have to put the medication into the bladder with a catheter. But also thereís the problem of having readily available the different compounds that you need to do one bladder instillation.
So what weíre looking at is if you can provide a solution where all the components are there, it makes it much easier for the physician or the clinician to instill the medications.
At the same time, theyíre very effective at giving acute relief of symptoms. In this sense, youíll see a great growth in the product more so because a), it works, and b) itís easy to use."