Dysport Wins Positive Opinion in Europe for Treating Bladder Issues

Dysport (abobotulinumtoxinA), a form of purified botulinum toxin, has received a positive opinion in Europe for managing urinary incontinence in adults with neurogenic detrusor overactivity (NDO), or overactive bladder.

The opinion is specifically for those who experience bladder issues due to multiple sclerosis (MS) or spinal cord injury, and who regularly require a catheter to drain urine and remove bladder pressure.

With this opinion, countries of the European Union can now grant marketing approval to Dysport at the national level. Ipsen, the company developing the injectable medication, is also trying to obtain approval in countries outside the EU, it announced in a press release.

Normally, the muscle of the bladder’s wall (detrusor muscle) remains relaxed to allow the bladder to fill with urine, and tightens during urination to empty it. The instructions to either relax or tighten are given by the nerves carrying messages from the spinal cord to the bladder.

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In patients with MS, however, the nerves can become damaged and less efficient at transmitting electrical signals. When the communication between the spinal cord and the bladder is thrown into disarray, this can result in neurogenic detrusor overactivity, leading to an overactive detrusor muscle that increases pressure and causes unexpected and frequent urine leakage.

Dysport is a form of botulinum toxin type A approved in MS for easing abnormal muscle stiffness (spasticity) in the upper and lower limbs. It works by blocking the nerve signals to the muscle in which it’s injected. Without those signals, the muscle is not able to tighten.

Studies have shown Dysport, injected into the detrusor muscle, reduced urinary incontinence due to NDO in patients with MS or spinal cord injury.

Ipsen launched two international Phase 3 clinical trials — CONTENT1 (NCT02660138) and CONTENT2 (NCT02660359) — which included 485 patients with urinary incontinence due to MS or spinal cord injury.

The patients were regularly undergoing clean intermittent catheterization (CIC), a procedure to empty the bladder with a catheter, and did not respond well to oral anticholinergic medications. About 30% had NDO due to MS; the remaining had spinal cord injury.

Participants were randomly assigned to receive one of two Dysport doses — 600 or 800 units — or a placebo, injected into the detrusor muscle. They could request additional treatment if more than 12 weeks had passed since their last injection. They were followed for up to 104 weeks.

The application requesting Dysport’s approval included pooled data from these trials. Results were recently reported in a study, “Efficacy and safety of abobotulinumtoxinA in patients with neurogenic detrusor overactivity incontinence performing regular clean intermittent catheterization: pooled results from two Phase 3 randomized studies (CONTENT1 and CONTENT2),” published in European Urology.

The trials met their primary goal of reducing the number of urinary incontinence episodes per week. After six weeks, patients on the placebo had a 12.7 reduction in their average number of weekly episodes, compared to average reductions of more than 22 episodes a week in the Dysport groups.

Dysport also significantly increased the volume of urine per void, by more than 80 mL over the six weeks, compared with a reduction of 5.9 mL per void in the placebo group.

The reduction in urinary incontinence translated into better quality of life (QoL), measured using the 22-item Incontinence-QoL (I-QoL) questionnaire. More than 60% of the Dysport-treated patients had an 11 point or greater increase in their I-QoL scores at six weeks, versus 32% in the placebo group.

More than 40% of patients on the active group did not receive any additional Dysport treatment, meaning their benefits were derived from a single injection.

The treatment was well-tolerated overall. Urinary infection was the most common side effect, but its frequency was similar among the three groups. The proportion of treatment-emergent side effects was also comparable across groups and there were no serious treatment-related side effects.

“[Dysport] injections improved their symptoms and bladder function, with no unexpected effects,” the researchers wrote.

Based on these findings, Dysport may provide “an effective treatment and alternative option for patients with [NDO] who have an inadequate response to oral anticholinergics and are already performing CIC,” the team concluded.