Eliapixant might not reduce clinical outcomes in Overactive Bladder: OVADER Trial

Overactive bladder (OAB) syndrome is a chronic medical condition that majorly influence the patients quality of life in a significant amount of the population. OAB affects performance of daily activities and has an estimated prevalence of 16.5%. Not much Effective, well-tolerated novel treatments for overactive bladder (OAB) is known. The P2X3 receptor antagonist eliapixant demonstrated potential to reduce OAB symptoms in preclinical studies.

A recent trial OVADER was not able to effeciently meet clinically desired outcomes . OAB continues to be a misunderstood condition from a pathophysiological viewpoint. Meanwhile, it suggests clinicians seeing patients for OAB should follow European clinical guidelines, including a medical history and full physical examination, validated questionnaire, bladder diary, and urinalysis. The findings of the trial are published in European Urology.

Researchers aimed to evaluate the safety, tolerability, and efficacy of eliapixant in patients with OAB with urgency urinary incontinence (UUI). OVADER trial was a 12-wk, randomised, placebo-controlled, double-blind, parallel-group, multicentre, phase 2a study (NCT04545580) conducted between 2020 and 2022 in private and institutional clinical practices. Eligible patients were aged ≥18 yr with wet OAB symptoms (urgency, urinary frequency, and urinary incontinence) for ≥3 mo before screening. Randomisation (1:1 ratio) to oral eliapixant 125 mg or placebo twice daily.

The researchers looked for primary the mean change from baseline in the mean number of UUI episodes/24 h over weeks 4, 8, and 12 according to an electronic bladder diary, evaluated using a repeated-measurement model in a Bayesian framework.

The key findings of the trial are

• A total of 202 patients enrolled, 85 were valid for per-protocol analysis. The primary efficacy endpoint was not met.

• 100 patients were randomly assigned, 51 in eliapixant group 125 mg; 49 in placebo group twice daily, and the study was completed by 81 patients (40 in eliapixant and 41 in placebo).

• The majority of patients were female, mean age was 58.8 years, and prior to screening, they had experienced OAB for a mean of 95.5 months.

• The posterior probability for eliapixant superiority over placebo was 40% (point estimate 0.05, 95% credible interval −∞ to 0.38), which did not meet the predefined criterion of ≥90% probability.

• Secondary and exploratory endpoints were not met. The incidence of adverse events was similar in the eliapixant group of 32 patients, i.e 63% and placebo group of 27 i.e 56% most were mild and five led to discontinuation of eliapixant.

Researchers concluded that “OVADER did not meet its clinical efficacy endpoints. Potential reasons include the nonspecific OAB symptom complex, the poorly understood pathophysiology, and the coinciding COVID-19 pandemic.”

Reference: Flavio Ewerton, Francisco Cruz, Moritz Kapp, Stefan Klein; Efficacy and Safety of Eliapixant in Overactive Bladder: The 12-Week, Randomised, Placebo-controlled Phase 2a OVADER Study; August 08, 2023 DOI:https://doi.org/10.1016/j.euf.2023.07.008.