Liposomal Botulinum Toxin Shows Promise in Treating Refractory Overactive Bladder

By Bridgett Novak

NEW YORK - Intravesical instillation of liposomal onabotulinumtoxinA may be a promising, minimally-invasive approach for treatment of refractory overactive bladder (OAB), according to a new study.

Researchers found a simple liquid instillation of the medication significantly improved micturition frequency and urgency symptoms compared with placebo, without the need for multiple needle injections and the associated risk of urinary retention.

The findings were presented May 17 at the annual meeting of the American Urological Association in Orlando.

Most people with idiopathic OAB are treated with antimuscarinic pills. For patients who are unresponsive, options include sacral neuromodulation, percutaneous tibial nerve stimulation and intradetrusor injection of botulinum toxin.

"Intradetrusor injections are generally effective, but they require a cystoscopic procedure which involves local anesthesia and 20 to 30 needle injections and patients run an increased risk of urinary retention and UTIs," said Dr. Michael Chancellor, professor of urology at Oakland University's William Beaumont School of Medicine in Rochester, Michigan, and chief medical officer of Lipella Pharmaceuticals, which funded the new research.

The trial included 62 OAB patients (29 men and 33 women) with a mean micturition frequency of >8/day, urgency or urge incontinence episodes of >1/day and an urgency severity scale score of at least 2. Major exclusion criteria included bladder outlet obstruction, neurogenic bladder dysfunction, PVR volume >150 ml, and incontinence in which stress was the predominant factor.

Before being enrolled, all participants had received at least four weeks of antimuscarinic pills without improvement or with intolerable adverse effects.

Thirty-one patients were randomized to receive a single instillation of liposomal onabotulinumtoxinA (LP-09) 200 U solution; the other 31 received a 50 mL saline solution.

Urine frequency was reduced at the four-week checkpoint for 79% of those who received botulinum toxin compared to 56% in the saline group.

In terms of urgency severity scores, four subjects in the placebo group improved and four got worse. In the active-treatment group, 11 of the subjects improved and only one got worse. Neither group had problems with urinary retention.

"Frequency of urgency events also decreased with treatment, however these improvements did not reach statistical significance with respect to the placebo group," Dr. Chancellor told Reuters Health by email. "The results were also inconclusive on urge incontinence since the sample population had a relatively low baseline."

Dr. Roger Dmochowski, director of Pelvic Medicine and Reconstruction at Vanderbilt University Medical Center in Nashville, Tennessee, said in a statement about the findings that botulinum toxin A "is proving to be an effective solution for bladder disorders with patients experiencing little to no side effects, improved bladder function and potentially avoiding more invasive surgery options."

"However, longer-term follow-up and a larger number of patients are needed, along with more data regarding the safety of this treatment protocol," Dr. Dmochowski, who was not involved in the study, added in an email to Reuters Health.

Dr. Chancellor agreed: "The length of time of these effects is an important parameter. Any conclusion regarding duration will be better addressed with a future study, which is currently being planned."

Lipella provided liposomes for this study, as well as financial support for an independent CRO that provided subject randomization, site monitoring and data analysis.

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