Advances in Research to Treat Urological Disorders
SAN FRANCISCO, CA– July 8, 2002 – As the “baby boom” generation continues to age, scientists are pursuing medical advances that may someday lead to treating a variety of health conditions that are expected to impact this ever-growing population, including overactive bladder (OAB), stress urinary incontinence (SUI) and benign prostatic hyperplasia (BPH). In an announcement of new data being presented at the World Congress of Pharmacology in San Francisco this week, as well as at a satellite symposium just prior to the meeting, Roche demonstrates its ongoing progress in discovering and developing new therapies to address these conditions. Of note, preclinical data on P2X purinergic receptors, which are novel sensory neuronal targets for preventing urine storage disorders, indicate that antagonists have potential to treat OAB more effectively than currently approved treatments. At the quadrennial pharmacology meeting, Roche will present data on this and several other approaches that are part of the company’s promising research to treat genitourinary disorders. Some 5,000 researchers from throughout the world are expected to attend.
“Our longer-term approach to developing treatments for genitourinary diseases such as OAB is to target the mechanisms controlling urinary function, rather than merely suppressing the action of the bladder muscles,” said Anthony Ford, Ph.D., head of Genitourinary Research at Roche Bioscience in Palo Alto, Calif. “In other words, we are effectively targeting more of the ‘wiring’ instead of the ‘plumbing’, where we feel the problem occurs. The data that we are presenting at this meeting may represent important progress in targeting such prevalent conditions. It is our intent to treat patients so that they no longer suffer in silence or feel the need to limit their daily activities to avoid embarrassment.”
During the symposium, new data will be presented on the development of knockout mice to determine whether P2X2 and P2X3 receptors collectively control sensory neuron responses to bladder distention and irritation. These data extend earlier findings from 2000, when Roche scientists announced the creation of a knockout mouse that lacked the gene for a sensory neuron receptor, known as P2X3 .
They discovered that the absence of this receptor alters the control of urine storage and elimination, leading them to conclude that it plays a pivotal role in receiving signals from the filling bladder. Their research suggests that blocking this receptor may provide a more normal return to urinary control for the 35 million people who experience OAB than current treatment methods. “In our studies of these mice, we have observed that the greatest differences are evident compared with wild-type mice, under conditions of acute irritation or pathology,” said Dr. Ford.
Roche is currently developing P2X receptor products for the treatment of OAB, and believe that this approach may have broad impact, for example in other diseases such as cystitis and BPH.
Other OAB Studies
In two pre-clinical studies comparing an experimental antimuscarinic Roche compound to tolterodine and oxybutynin, the leading OAB treatments, the Roche product showed better bladder selectivity in animal models. The novel antimuscarinic reduced bladder overactivity yet imparted less impact on salivation or CNS function, the sites of common side effects of tolterodine and oxybutynin.
Other Genitourinary Research at Roche
Genitourinary research is a key emerging area for Roche. “This is a promising time for our genitourinary diseases R&D portfolio because so many advances are occurring,” said Dr. Ford. “We hope that our approaches to treating these disorders may change the way physicians currently look at these conditions in the years to come and provide a substantial improvement for patients.”
In the area of SUI, Roche is focusing its efforts on developing products to improve muscle tone of the urethra and bladder neck, rather than the current approach of minimizing leakage via devices or surgery. One such compound, R450, an alpha 1 adrenoceptor agonist is in Phase II development for the treatment of SUI and has been shown in Phase II trials to significantly decrease the frequency of incontinence episodes. This will represent a significant improvement for the more than 40 million patients worldwide who experience SUI.
In BPH, Roche’s short-term research focuses on relieving any urinary obstruction that may have occurred as a result of prostate enlargement and in relieving urgency and nighttime urination.. Over the long term, Roche is exploring mechanisms for reversing or preventing BPH altogether in the 36 million men worldwide who have the condition.
Other Roche Research at the World Pharmacology Congress
Roche scientists will also be presenting research advances in other therapeutic areas at the meeting. Much of the additional data to be presented centers around the central nervous system (CNS) and pre-clinical investigations Roche scientists are reporting relating to conditions such as psychosis, as well as on respiratory diseases research.
Roche Pipeline
Roche currently has 138 projects in research and 74 in development, including 48 new molecular entities (NMEs). This represents a 35 percent increase in the number of NMEs in Roche’s development portfolio over the past 12 months. Over the next five years Roche expects to file 17 new drug applications (NDAs) for products in a variety of key disease areas including oncology, HIV/AIDS, anxiety/depression, stress incontinence and rheumatoid arthritis. Over the last five years, the Pharma division has made major changes in the organizational structure and the processes to fuel the Roche pipeline. These changes are now delivering increased productivity in terms of quantity, quality and value.
About Roche Bioscience
Located in Palo Alto, Calif., Roche Bioscience is one of the company’s five pharmaceutical research centers. Researchers at Roche Bioscience focus on the discovery and early clinical development of innovative new medicines to treat diseases including arthritis, asthma and other respiratory diseases; human immunodeficiency virus (HIV) and hepatitis C virus; anxiety, depression, schizophrenia and other neuropsychiatric diseases; genitourinary diseases and osteoporosis. Roche has five global pharmaceutical research centers: Basel (Switzerland), Kamakura (Japan), Nutley (N.J.), Palo Alto (Calif.), and Penzberg (Germany).
For more information on Roche, access http://paloalto.roche.com.
