Treatments for overactive bladder are not one size fits all, which is why Urovant is advancing URO-902, an injectable gene therapy that is currently being investigated in Phase IIa clinical trials.
Courtesy of Urovant Sciences
The bathroom is already a place where people spend a lot of time but for some 33 million Americans, trips to the lavatory to urinate can consume hours of a day due to overactive bladder (OAB). Urovant Sciences is looking to make a difference in the lives of patients struggling with this disease with Gemtesa (vibegron), approved by the U.S. Food and Drug Administration in 2020 and URO-902, an investigational gene therapy.
Overactive bladder refers to a collection of symptoms that cause a person to feel the frequent and sudden urge to urinate, symptoms which may be difficult to control. People with OAB may pass urine more than eight times a day, the accepted standard for how many times a person should urinate over 24 hours, and could experience moments of incontinence. Additionally, people with the condition may wake up during the night to pass urine, which can cause issues with sleep. Overall, the symptoms can be devastating to a person’s quality of life.
“The interesting thing about overactive bladder is that when you look at the definition, ‘idiopathic overactive bladder’ - the condition is about having these symptoms and not having an identifiable known cause,” David Staskin, M.D., associate professor of urology at Tufts University School of Medicine and principal investigator on a recent Phase III trial of Gemtesa, said during an interview with BioSpace.
There are a variety of ways that physicians can choose to approach the treatment of OAB including behavioral interventions, such as reducing caffeine intake and managing fluid intake, pelvic floor physical therapy and pharmacological therapies, which come with their own set of drawbacks.
“There are many, many drugs on the market but whether you look at the newer or older ones, 70% of patients will quit using these drugs within a year. It’s usually because they don’t work well enough or they’re costly or they have significant side effects like confusion, constipation, dry mouth or high blood pressure,” Kenneth Peters, M.D., chief of the department of urology at Beaumont Hospital and principal investigator of Urovant’s Phase IIa trial of URO-902, told BioSpace.
Urovant, a biopharma company focused on developing treatments for urological disorders, is a leader in the OAB treatment space. The Irvine, California-based company markets Gemtesa, its first FDA-approved product. It is also developing URO-902, a novel gene therapy, for the same condition. Urovant presented updates and clinical trial results from both programs at the 2022 American Urological Association Meeting (AUA 2022) in May.
Gemtesa Continues to Impress at AUA 2022
Gemtesa is a selective beta 3 adrenergic receptor agonist that was approved by the FDA for the treatment of OAB in December 2020 based on data demonstrating the drug’s efficacy in reducing urgency episodes, urinary frequency and incontinence. The drug works by stimulating the beta 3 adrenergic receptors which cause the bladder to relax. Gemtesa is also extremely specific to beta 3, which is important because stimulating beta 1 receptors could lead to negative consequences for patients such as hypertension and tachycardia.
The results shared at AUA 2022 covered the long-term safety and efficacy of the therapeutic in patients with OAB. The primary endpoint was safety, measured by incidence of severe events, while secondary endpoints included changes from baseline in measures of daily urination, urge urinary incontinence (UUI) episodes, urgency and total urinary incontinence. At 52 weeks, Gemtesa was associated with sustained and patient-perceived meaningful improvements in OAB questionnaires as well as reductions from baseline in all secondary endpoints measured. Additionally, the analyses showed that the drug is effective in both men and women as well as patients over and under 65 years of age.
“In addition to efficacy, safety and side effects, we also looked to see if the objective improvements that we are statistically measuring made a difference in people’s lives - in their quality of life. We found that there was a correlation, that patients really did improve significantly in measures of their quality of life,” Staskin said.
Gemtesa also offers benefits in comparison to other OAB treatments on the market, he noted. For one, beta 3 agonists are not associated with cognitive issues which can sometimes be seen in elderly people that take anti-cholinergic or anti-muscarinic drugs to control the condition.
Up next for this program is an advanced study investigating the drug’s efficacy in men with enlarged prostates who have received other treatments but still experience residual OAB symptoms. Additionally, the drug may be investigated in pediatric populations as well as in other indications.
A Novel Approach
Treatments for OAB are not one size fits all, which is why Urovant is also advancing URO-902, an injectable gene therapy that is currently being investigated in Phase IIa clinical trials.
The gene therapy is injected into the bladder wall where it then integrates itself into the cells and expresses an alpha subunit of the human BK channel, a calcium-activated potassium channel. By increasing the number of these potassium channels and their movement, the therapy is able to reduce the spasming of the bladder, thereby correcting some of the dysfunction of an overactive bladder.
“This is the first-ever report of using this type of gene therapy in a controlled clinical trial. There were two really important things looked at in this trial. One was safety, obviously, and what we found is that it’s an incredibly safe treatment. There were no significant serious adverse events,” Peters said. “We were also hoping to see that the therapy did not lead to significant urinary retention, in other words, relaxing the bladder so much that you can’t urinate. Although one patient in the trial experienced this, the problem resolved itself on its own within four weeks.”
The trial demonstrated that the therapy was associated with clinically relevant improvement in mean daily urination, urgency episodes and urge urinary incontinence. Patients also reported that they felt the treatment improved their condition, an important measure of patient satisfaction with the therapy. Notably, patients included in the trial were those who had previously failed oral OAB therapies.
Notably, Peters said that the improvement hadn’t yet plateaued, meaning it’s possible that the gene therapy could provide a durable and lasting response with just one dose.
The gene therapy also offers unique benefits for patients.
“This could be an office-based treatment that keeps people out of the operating room for implantable devices. Remember, overactive bladder affects more than 30 million Americans – it’s a huge problem,” Peters said. “Second, this type of therapy may be safer than the alternatives that are out there, like those with side effects that prevent people from wanting to try something like botulinum toxin (botox). Being that it is a gene therapy, it becomes integrated into your cellular structure and it should last a fair amount of time, which we will see as we continue to assess the longevity of it.”
Urovant will continue to analyze long-term data for URO-902 and is looking forward to the full data readout from the 48-week trial. The company will continue to evaluate the therapy’s long-term effectiveness, and hopefully, in the future, the next steps will include a pivotal trial to garner FDA approval.
Featured Jobs on BioSpace
