An Evaluation of the Efficacy and Safety of Vibegron in the Treatment of Overactive Bladder

Figures & data

Table 1 Overview of Primary Vibegron Studies

Study	Study Duration	Study Type	Experimental Group*	Control Group*	Outcomes Assessed
Staskin et al 2020^Citation16 EMPOWUR	12 wk	Phase 3	Vibegron 75 mg (N=545)	Placebo (N=540) Tolterodine 4 mg ER (N=430)	Number of micturitions, UUI episodes,^† urgency episodes, volume voided, proportion of patients with ≥75% reduction in UUI episodes^† Safety
Staskin et al 2021^Citation30 EMPOWUR Extension	52 wk	Phase 3, extension	Vibegron 75 mg (N=273)	Tolterodine 4 mg ER (N=232)	Micturitions, urgency episodes, UUI episodes,^† total urinary incontinence episodes^† Safety
Weber et al 2021^Citation31	28 d	Phase 1, ambulatory blood pressure monitoring	Vibegron 75 mg (N=106)	Placebo (N=108)	Mean daytime and 24-hour ambulatory systolic blood pressure, diastolic blood pressure, and heart rate Safety

Notes: *Population numbers reported from the safety set, defined as all patients who received ≥1 dose of double-blind study medication. ^†In patients with OAB wet (defined as an average of ≥8 micturitions and ≥1 UUI episode per day).

Abbreviations: ER, extended release; OAB, overactive bladder; UUI, urge urinary incontinence.

Table 2 Overview of Secondary, Post Hoc, and Subgroup Analyses of EMPOWUR

Publication	Analysis	Experimental Group	Control Group	Outcomes Assessed
Frankel et al 2020^Citation32	Patient-reported QoL outcomes	Vibegron 75 mg (N=526)	Placebo (N=520) Tolterodine 4 mg ER (N=417)	OAB-q, PGI
Varano et al 2021^Citation33	Older adults (≥65 years old, ≥75 years old)	≥65 years old Vibegron 75 mg (N=242) ≥75 years old Vibegron 75 mg (N=75)	≥65 years old Placebo (N=220) Tolterodine 4 mg ER (N=166) ≥75 years old Placebo (N=57) Tolterodine 4 mg ER (N=47)	Micturitions, urgency episodes, UUI episodes* Responder analyses: Percentage of patients with ≥75% reduction in UUI episodes* and with ≥50% reduction in urgency episodes Safety
Staskin et al 2021^Citation30	Efficacy in OAB wet vs dry	OAB wet Vibegron 75 mg (N=403) OAB dry Vibegron 75 mg (N=123)	OAB wet Placebo (N=405) Tolterodine 4 mg ER (N=319) OAB dry Placebo (N=115) Tolterodine 4 mg ER (N=98)	Urgency episodes, micturitions
Varano et al 2021^Citation36	Efficacy and safety in women	Vibegron 75 mg (N=463)	Placebo (N=459) Tolterodine 4 mg ER (N=364)	Micturitions, urgency episodes, UUI episodes* Safety

Notes: *In patients with OAB wet (defined as an average of ≥8 micturitions and ≥1 UUI episode per day).

Abbreviations: ER, extended release; OAB, overactive bladder; OAB-q, OAB questionnaire; PGI, patient global impression; QoL, quality of life; UUI, urge urinary incontinence.

Figure 1 LS mean change from baseline in average daily number of (A) micturitions and (B) UUI episodes over 12 weeks. *P < 0.05. **P < 0.01. ***P < 0.001 vs placebo. Reprinted with permission from Wolters Kluwer Health, Inc.: Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN, Jr. International phase III, randomized, double-blind, placebo and active controlled study to evaluate the safety and efficacy of vibegron in patients with symptoms of overactive bladder: EMPOWUR. J Urol. 2020;204(2):316–324. Available from: https://www.auajournals.org/doi/10.1097/JU.0000000000000807.¹⁶

Abbreviations: LS, least squares; UUI, urge urinary incontinence.

Table 3 Key Patient Baseline Demographics and Clinical Characteristics of Patients ≥65 Years Old (a Subpopulation Analysis from the EMPOWUR Trial)

Characteristic	Placebo	Vibegron 75 mg	Tolterodine 4 mg ER	Overall
Full Analysis Set, N	220	242	166	628
Women, n (%)	178 (80.9)	204 (84.3)	132 (79.5)	514 (81.8)
Men, n (%)	42 (19.1)	38 (15.7)	34 (20.5)	114 (18.2)
Mean (SD) age, y	71.8 (5.39)	71.8 (5.59)	72.0 (5.43)	71.9 (5.47)
Age ≥75 y, n (%)	57 (25.9)	75 (31.0)	47 (28.3)	179 (28.5)
Race, n (%)
White	176 (80.0)	197 (81.4)	129 (77.7)	502 (79.9)
Black or African American	19 (8.6)	26 (10.7)	19 (11.4)	64 (10.2)
Asian	23 (10.5)	19 (7.9)	17 (10.2)	59 (9.4)
Other	2 (0.9)	0	1 (0.6)	3 (0.5)
Region, n (%)
US	190 (86.4)	218 (90.1)	150 (90.4)	558 (88.9)
Non-US	30 (13.6)	24 (9.9)	16 (9.6)	70 (11.1)
Safety Set,* N	228	246	171	645
Medical history (conditions of interest), n (%)
Hypertension^†	134 (58.8)	155 (63.0)	120 (70.2)	409 (63.4)
Osteoarthritis	64 (28.1)	76 (30.9)	59 (34.5)	199 (30.9)
Gastroesophageal reflux	59 (25.9)	65 (26.4)	48 (28.1)	172 (26.7)
Diabetes mellitus	12 (5.3)	15 (6.1)	10 (5.8)	37 (5.7)
Concomitant non-OAB medications,^‡ n (%)
Agents acting on the renin-angiotensin system	99 (43.4)	112 (45.5)	81 (47.4)	292 (45.3)
Lipid-modifying agents	96 (42.1)	101 (41.1)	80 (46.8)	277 (42.9)
Vitamins	87 (38.2)	89 (36.2)	59 (34.5)	235 (36.4)

Notes: *Patients in the safety set were excluded from the full analysis set for one or more reasons (ie, they did not have a baseline or ≥1 post-baseline micturition assessment or they did not receive double-blind study medication). ^†Pre-existing hypertension was based on baseline vitals and medical history. ^‡Within the past 12 months.

Abbreviations: ER, extended release; OAB, overactive bladder.

Figure 2 LS mean change from baseline in average daily number of UUI episodes over 52 weeks. *P < 0.05. Reprinted with permission from Wolters Kluwer Health, Inc.: Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN, Jr. Once-daily vibegron 75 mg for overactive bladder: long-term safety and efficacy from a double-blind extension study of the international phase 3 trial (EMPOWUR). J Urol. 2021;205(5):1421–1429. Available from: https://www.auajournals.org/doi/10.1097/JU.0000000000001574.³⁰

Abbreviations: LS, least squares; ER, extended release.

Figure 3 LS mean change from baseline in average daily number of (A) urgency episodes and (B) total urinary incontinence episodes over 52 weeks. *P < 0.05. Reprinted with permission from Wolters Kluwer Health, Inc.: Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN, Jr. Once-daily vibegron 75 mg for overactive bladder: long-term safety and efficacy from a double-blind extension study of the international phase 3 trial (EMPOWUR). J Urol. 2021;205(5):1421–1429. Available from: https://www.auajournals.org/doi/10.1097/JU.0000000000001574.³⁰

Abbreviations: LS, least squares; ER, extended release.

Table 4 Adverse Events by Treatment Group in the EMPOWUR Trial (Safety Analysis Set)

	Placebo	Vibegron	Tolterodine
No. pts	540	545	430
No. summary (%)
Any AE	180 (33.3)	211 (38.7)	166 (38.6)
Any AE of clinical interest	40 (7.4)	36 (6.6)	38 (8.8)
Any serious AE	6 (1.1)	8 (1.5)	10 (2.3)
Any AE leading to treatment discontinuation	6 (1.1)	9 (1.7)	14 (3.3)
No. by AE preferred term (%)*
Urinary tract infection	33 (6.1)	27 (5.0)	25 (5.8)
Headache	13 (2.4)	22 (4.0)	11 (2.6)
Nasopharyngitis	9 (1.7)	15 (2.8)	11 (2.6)
Diarrhea	6 (1.1)	12 (2.2)	9 (2.1)
Nausea	6 (1.1)	12 (2.2)	5 (1.2)
Upper respiratory tract infection	4 (0.7)	11 (2.0)	2 (0.5)
Constipation	7 (1.3)	9 (1.7)	6 (1.4)
Dry mouth	5 (0.9)	9 (1.7)	28 (6.5)
Hypertension	9 (1.7)	9 (1.7)	11 (2.6)
Dizziness	6 (1.1)	5 (0.9)	4 (0.9)
Blood pressure increased	5 (0.9)	4 (0.7)	8 (1.9)
Urinary retention	2 (0.4)	3 (0.6)	3 (0.7)
Fatigue	5 (0.9)	2 (0.4)	6 (1.4)
Alanine aminotransferase increased	2 (0.4)	1 (0.2)	1 (0.2)
Aspartate aminotransferase increased	1 (0.2)	1 (0.2)	1 (0.2)
Cardiac failure congestive	0	1 (0.2)	0
Cerebrovascular accident	0	1 (0.2)	1 (0.2)
Cystitis	1 (0.2)	1 (0.2)	1 (0.2)
Hypotension	1 (0.2)	1 (0.2)	1 (0.2)
Blood pressure diastolic increased	0	0	1 (0.2)
Chest pain	3 (0.6)	0	0
Escherichia urinary tract infection	0	0	1 (0.2)
Pollakiuria	1 (0.2)	0	0
Syncope	2 (0.4)	0	1 (0.2)

Notes: *Includes all AEs with an incidence of 2.0% or greater in the vibegron group and greater than for placebo, plus all protocol-defined AEs of clinical interest. Reprinted with permission from Wolters Kluwer Health, Inc.: Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN, Jr. International phase III, randomized, double-blind, placebo and active controlled study to evaluate the safety and efficacy of vibegron in patients with symptoms of overactive bladder: EMPOWUR. J Urol. 2020;204(2):316–324. Available from: https://www.auajournals.org/doi/10.1097/JU.0000000000000807.¹⁶

Abbreviation: AE, adverse event.

Table 5 Adverse Events by Treatment Group in the EMPOWUR Extension Trial (Safety Set Extension)

	Vibegron	Tolterodine
No. pts	273	232
No. ≥1 treatment-emergent AE (%)	171 (62.6)	126 (54.3)
No. discontinued study medication due to AE	4 (1.5)	8 (3.4)
No. ≥1 treatment-emergent SAE (%)	9 (3.3)	10 (4.3)
No. SAEs resulting in death (%)	1 (0.4)*	0
No. SAEs considered treatment-related by investigator^†	1 (0.4)	2 (0.9)
No. AEs >2% in either treatment group (%)
Hypertension^‡	24 (8.8)	20 (8.6)
Urinary tract infection	18 (6.6)	17 (7.3)
Headache	15 (5.5)	9 (3.9)
Diarrhea	13 (4.8)	4 (1.7)
Nasopharyngitis	13 (4.8)	12 (5.2)
Constipation	10 (3.7)	6 (2.6)
Nausea	10 (3.7)	7 (3.0)
Upper respiratory tract infection	10 (3.7)	1 (0.4)
Bronchitis	8 (2.9)	3 (1.3)
Anemia	7 (2.6)	2 (0.9)
Hyperglycemia	7 (2.6)	2 (0.9)
Residual urine volume increased	7 (2.6)	3 (1.3)
Back pain	6 (2.2)	3 (1.3)
Musculoskeletal pain	6 (2.2)	1 (0.4)
Dry mouth	5 (1.8)	12 (5.2)

Notes: *Arteriosclerotic disease, judged not related to the study drug by investigators and sponsor. ^†Vibegron: collagenous colitis; tolterodine: syncope and cardiac failure. ^‡Defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg (or both) at 2 consecutive visits in patients without baseline hypertension; an increase in SBP by ≥20 mm Hg or DBP by ≥10 mm Hg at 2 consecutive visits in patients with baseline hypertension; or the initiation of or increase in dose of medication for the treatment of hypertension in any patient. Reprinted with permission from Wolters Kluwer Health, Inc.: Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN, Jr. Once-daily vibegron 75 mg for overactive bladder: long-term safety and efficacy from a double-blind extension study of the international phase 3 trial (EMPOWUR). J Urol. 2021;205(5):1421–1429. Available from:https://www.auajournals.org/doi/10.1097/JU.0000000000001574.³⁰

Abbreviations: AE, adverse event; DBP, diastolic blood pressure; SAE, serious adverse event; SBP, systolic blood pressure.

Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN Jr. International phase III, randomized, double-blind, placebo and active controlled study to evaluate the safety and efficacy of vibegron in patients with symptoms of overactive bladder: EMPOWUR. J Urol. 2020;204(2):316–324. doi:10.1097/JU.0000000000000807

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Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN Jr. Once-daily vibegron 75 mg for overactive bladder: long-term safety and efficacy from a double-blind extension study of the international phase 3 trial (EMPOWUR). J Urol. 2021;205(5):1421–1429. doi:10.1097/JU.0000000000001574

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Weber M, White WB, King J, Walker A, Mudd PN, Haag-Molkenteller C. Effects of vibegron on ambulatory blood pressure in patients with overactive bladder: results from a double-blind study. Blood Pressure Monitoring. 2021;Epub ahead of print. doi:10.1097/MBP.0000000000000572

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Frankel J, Varano S, Staskin D, Shortino D, Jankowich R, Mudd PN Jr. Vibegron improves quality-of-life measures in patients with overactive bladder: patient-reported outcomes from the EMPOWUR study. Int J Clin Pract. 2021;75(5):e13937. doi:10.1111/ijcp.13937

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Varano S, Staskin D, Frankel J, Shortino D, Jankowich R, Mudd PN Jr. Efficacy and safety of once-daily vibegron for treatment of overactive bladder in patients aged ≥65 and ≥75 years: subpopulation analysis from the EMPOWUR randomized, international, phase III study. Drugs Aging. 2021;38(2):137–146. doi:10.1007/s40266-020-00829-z

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Varano S, Newman D, Shortino D, Jankowich R, Mudd PN Jr. Efficacy and safety of vibegron for the treatment of overactive bladder in women: a subgroup analysis from the EMPOWUR trial. Proceedings of the International Urogynecological Association Virtual; December 9–12, 2021.

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