Astellas Pharma Inc. announced results from its phase 3b BESIDE clinical trial demonstrated solifenacin (SOLI) with mirabegron (MIRA) as an add-on therapy (ADD-ON) was superior to solifenacin monotherapy in incontinent overactive bladder (OAB) patients.

The results of the BESIDE trial, which were presented at the 2015 annual meeting of the American Urological Association (AUA), showed that the ADD-ON group achieved its primary efficacy endpoints.    

In the BESIDE trial, the mean number of daily incontinence episodes was reduced by 1.80 episodes in OAB patients given solifenacin 5 mg with mirabegron 50 mg (dosage was increased from 25 mg after 4 weeks) as an add-on therapy compared to a reduction of 1.53 episodes seen with SOLI 5 mg monotherapy. The difference between the two treatments of approximately 0.26 was statistically significant (P=0.001). The mean number of daily micturitions was reduced by 1.59 micturitions in the ADD-ON group compared to 1.14 micturitions with SOLI 5 mg (the difference of 0.45 was statistically significant [P<0.001]).

In addition, ADD-ON treatment was both non-inferior and superior to SOLI 10 mg for daily reduction in micturitions. ADD-ON treatment also was superior to SOLI 5 mg and 10 mg monotherapy for improvement in urine volume voided per micturition.

At least one treatment emergent adverse event (TEAE) was reported by 35.9% receiving ADD-ON therapy, 39.4% receiving SOLI 10 mg and 33.1% receiving SOLI 5 mg, with the most common (occurring in at least 2% of patients) being dry mouth, constipation and peripheral edema. Serious adverse events (SAEs) were reported by 1.8% of patients receiving ADD-ON therapy, 2.1% receiving SOLI 10 mg and 1.2% receiving SOLI 5 mg. The ADD-ON group reported a lower incidence of dry mouth than the SOLI 10 mg group (5.9% versus 9.5%), and a similar incidence as the SOLI 5 mg group (5.6%). The incidence of constipation in the ADD-ON group was 4.6% versus 4.7% and 3.0% for the SOLI 10 mg and SOLI 5 mg groups, respectively.

"The BESIDE results appear to indicate that adding mirabegron therapy, a Beta-3 adrenergic agonist, to solifenacin therapy, an antimuscarinic, may offer relief from the burden of OAB," said Professor Marcus Drake, MA, DM, FRCS (Urol), University of Bristol and Bristol Urological Institute, Bristol, UK. "Such a combined use may help practitioners address the continued unmet need for additional treatment options that can help people living with this debilitating condition."

The Phase 3b BESIDE study is a randomized, double-blind, international study designed to evaluate the efficacy and safety of mirabegron as add-on therapy to solifenacin in incontinent OAB patients. Study patients received SOLI 5 mg monotherapy for 4 weeks; subjects with inadequate response to treatment (i.e., patients who still experienced one or more incontinence episodes during a three-day diary period) were then randomized to either SOLI 5 mg, SOLI 10 mg, or SOLI 5 mg in combination with MIRA 25 mg, which was increased to MIRA 50 mg after 4 weeks. Overall 2,174 patients were randomized to the ADD-ON group (n=727), SOLI 5 mg (n=728) or SOLI 10 mg (n=719). The primary efficacy endpoint was change from baseline to the end of treatment (EoT) in mean number of incontinence episodes/24 hours.

All three treatment arms investigated in this study appeared to be well-tolerated, and the adverse event (AE) profile with ADD-ON treatment was generally consistent with the known profiles of SOLI and MIRA. Vital signs in this group showed no additive or synergistic effects beyond those known for either monotherapy.

Myrbetriq/Betmiga/Betanis (mirabegron) is a beta-3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.

VESIcare (solifenacin succinate) tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. The recommended dose of VESIcare is 5 mg once daily. If the 5-mg dose is well tolerated, the dose may be increased to 10 mg once daily.

Myrbetriq,  Betmiga,  Betanis and VESIcare are trademarks of Astellas Pharma Inc.

Overactive bladder is a urine storage problem of urgency, with or without urge urinary incontinence (leakage), often with urinary frequency and nocturia.  By 2018, an estimated 546 million people worldwide will be affected by OAB.   For people with OAB, inappropriate signals are sent to the muscles in the bladder causing them to contract before the bladder is full. These bladder contractions may cause strong, sudden urges, and a frequent need to go to the bathroom.

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