January 1, 2010 (Vol. 30, No. 1)

Firm’s Technology Was Derived from Decades of Hands-On Clinical Exposure to Bladder Problems

Take an aging population with its increased incidence of urological disorders, add growing awareness of technological advances and new drug therapies, combine all of that with many years of research into bladder problems, and you get Urigen Pharmaceuticals, a specialty pharmaceutical company focused on the development and commercialization of treatments for urological disorders.

C. Lowell Parsons, M.D., has spent the last 35 years doing research on interstitial cystitis (IC), also known as lower urinary dysfunctional epithelium (LUDE), a painful bladder syndrome (PBS). According to Dr. Parsons, IC, which is caused by a leaky epithelium, can be misdiagnosed as a bladder infection or endometriosis.

“Mucus regulates the leakiness or permeability of the bladder,” explains Dr. Parsons, a professor of surgery/urology at the University of California San Diego (UCSD) Medical Center. “Interstitial cystitis—caused by defective mucus—is characterized by frequency, urgency, pain, and incontinence. 

“Defective mucus allows the potassium to leak through the mucus into the bladder wall. Potassium levels can contribute to the problem.” Dr. Parsons claims to have developed the first new test for IC in 70 years—the Potassium Sensitivity Test.

“PBS/IC is caused by 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,” he explains.

“These spasms trigger responses to urinate, resulting in pelvic pain, urgency, and frequency, the collection of symptoms associated with this disease. Once established, PBS can be a chronic disease, which can persist throughout life and have a devastating impact on the quality of life.”

Over the past 25 years, more than 7,000 women and men who have IC/LUDE have come to Dr. Parsons’ clinic at UCSD for care. He has received numerous federal and private grants for his research studies, and he has developed methods for detecting and treating IC/LUDE that are now in use around the world, he reports.

“While the initial onset of IC is not age-related, it causes long-term damage as one gets older,” Dr. Parsons explains. “It also gets worse after menopause, and it’s 40 percent genetically based. The condition affects one-quarter of all women.”

Dr. Parsons, who at one time treated IC surgically, learned years ago that heparin and Elmiron® (pentosan polysulfate sodium) could restore bladder function. “These drugs restore function, but don’t treat the symptoms,” he says, so he began using lidocaine to control the pain. “By adding sodium bicarbonate to the lidocaine and heparin, the treatment, which is administered with a catheter, penetrated the barriers of the bladder wall and provided instant relief.”

As he was developing this methodology, Dr. Parsons met William J. Garner, M.D. Urigen Pharmaceuticals was founded in 2005, and Dr. Parsons’ treatment regimen received a patent shortly thereafter. Initial funding came from private investors. While the company is headquartered in San Francisco, Dr. Parsons maintains his medical practice and teaching position in San Diego.

URG101, one of the company’s lead products, targets PBS/IC, which affects approximately 10.5 million men and women in North America. URG101 can address the underlying disease process while also providing acute symptom relief, unlike other treatments available, according to Dr. Parsons.

Urigen filed an IND in 2005 to initiate a Phase IIb multicenter, 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. While URG101 did not meet the primary endpoint in the study because of a problem in importing the heparin, the clinical trial achieved a high level of statistical significance on improvement in urgency.

In a subsequent Phase II multicenter, 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. Additionally, the study demonstrated improvement in average daytime pain and improvement in daytime urgency, Dr. Parsons says.

The company is working on fundraising for a Phase III trial for URG101. After that is completed, Dr. Parsons anticipates that the treatment will be on the market in two to three years.

Another lead product, URG301, is under development to control urinary urgency. This product, which is delivered via suppository, targets acute urgency in females diagnosed with an overactive bladder.

“We’ve made a lot of progress in making people feel better right away and improving their quality of life,” Dr. Parsons explains. “The biggest challenge today is to get people to realize what they have. Once they get the right diagnosis, we can treat their PBS/IC problems.”

Urine contains toxins and electrolytes (including K+), which can damage exposed urothelium and activate nerves.

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