These Highlights Do Not Include All The Information Needed To Use Gemtesa®

GEMTESA is indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adult males on pharmacological therapy for benign prostatic hyperplasia (BPH).

There is no experience with inadvertent GEMTESA overdosage. In case of suspected overdose, treatment should be symptomatic and supportive.

Vibegron is a selective beta-3 adrenergic agonist. The chemical name is (6S)-N-[4-[[(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl]methyl]phenyl]-4-oxo-7,8-dihydro-6H-pyrrolo[1,2-a]pyrimidine-6-carboxamide having a molecular formula of C₂₆H₂₈N₄O₃ and a molecular weight of 444.538 g/mol. The structural formula of vibegron is:

Vibegron is a crystalline, white to off-white to tan powder.

GEMTESA tablets, for oral administration contain 75 mg of vibegron and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, mannitol, and microcrystalline cellulose. The light green film coating contains FD&C Blue No. 2 - aluminum lake, hypromellose, iron oxide yellow, lactose monohydrate, titanium dioxide, and triacetin.

Angioedema of the face and/or larynx has been reported with GEMTESA. Angioedema has been reported to occur hours after the first dose or after multiple doses. Angioedema, associated with upper airway swelling, may be life-threatening. If involvement of the tongue, hypopharynx, or larynx occurs, immediately discontinue GEMTESA and provide appropriate therapy and/or measures necessary to ensure a patent airway. GEMTESA is contraindicated in patients with known hypersensitivity to vibegron or any component of GEMTESA [see Contraindications (4) and Adverse Reactions (6.2)].

The safety and effectiveness of GEMTESA in pediatric patients have not been established.

Of 526 patients who received GEMTESA in the clinical studies for OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency, 242 (46%) were 65 years of age or older, and 75 (14%) were 75 years of age or older [see Clinical Studies (14.1)]. No overall differences in safety or effectiveness of GEMTESA have been observed between patients 65 years of age and older and younger adult patients.

Of the total number of GEMTESA-treated patients in clinical studies for OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency in adult males on pharmacological therapy for benign prostatic hyperplasia (BPH), 347 (63%) were 65 years of age and older, while 100 (18%) were 75 years of age and older [see Clinical Studies (14.2)]. No overall differences in safety of GEMTESA have been observed between patients 65 years of age and older and younger adult patients.

GEMTESA is contraindicated in patients with known hypersensitivity to vibegron or any components of GEMTESA. Hypersensitivity reactions, such as angioedema, have occurred [see Warnings and Precautions (5.2) and Adverse Reactions (6.2)].

The following clinically significant adverse reaction is described elsewhere in the labeling:

• Urinary retention [see Warnings and Precautions (5.1)]

Concomitant use of GEMTESA increases digoxin maximal concentrations (C_max) and systemic exposure as assessed by area under the concentration-time curve (AUC) [see Clinical Pharmacology (12.3)]. Serum digoxin concentrations should be monitored before initiating and during therapy with GEMTESA and used for titration of the digoxin dose to obtain the desired clinical effect. Continue monitoring digoxin concentrations upon discontinuation of GEMTESA and adjust digoxin dose as needed.

No dosage adjustment for GEMTESA is recommended for patients with mild, moderate, or severe renal impairment (eGFR 15 to <90 mL/min/1.73 m²). GEMTESA has not been studied in patients with eGFR <15 mL/min/1.73 m² (with or without hemodialysis) and is not recommended in these patients [see Clinical Pharmacology (12.3)].

Vibegron's exposure-response relationship and the time course of pharmacodynamic response are not fully characterized.

Mean vibegron C_max and AUC increased in a greater than dose-proportional manner up to 600 mg (8 times the approved recommended dosage). Steady state concentrations are achieved within 7 days of once daily dosing. The mean accumulation ratio (R_ac) was 1.7 for C_max and 2.4 for AUC_0-24hr.

Urinary retention has been reported in patients taking GEMTESA. The risk of urinary retention may be increased in patients with bladder outlet obstruction and also in patients taking muscarinic antagonist medications for the treatment of OAB. Monitor patients for signs and symptoms of urinary retention, particularly in patients with bladder outlet obstruction or patients taking muscarinic antagonist medications for the treatment of OAB. Discontinue GEMTESA in patients who develop urinary retention [see Adverse Reactions (6.1)].

The recommended dosage of GEMTESA is one 75 mg tablet orally, once daily with or without food. Swallow GEMTESA tablets whole with a glass of water.

In adults, GEMTESA tablets also may be crushed, mixed with a tablespoon (approximately 15 mL) of applesauce and taken immediately with a glass of water [see Clinical Pharmacology (12.3)].

No dosage adjustment for GEMTESA is recommended for patients with mild to moderate hepatic impairment (Child-Pugh A and B). GEMTESA has not been studied in patients with severe hepatic impairment (Child-Pugh C) and is not recommended in this patient population [see Clinical Pharmacology (12.3)].

GEMTESA is a beta-3 adrenergic agonist indicated for the treatment of:

• overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults. (1.1)
• overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adult males on pharmacological therapy for benign prostatic hyperplasia (BPH). (1.2)

Vibegron is a selective human beta-3 adrenergic receptor agonist. Activation of the beta-3 adrenergic receptor increases bladder capacity by relaxing the detrusor smooth muscle during bladder filling.

Urinary Retention: Monitor for urinary retention, especially in patients with bladder outlet obstruction and also in patients taking muscarinic antagonist medications for OAB, in whom the risk of urinary retention may be greater. If urinary retention develops, discontinue GEMTESA. (5.1)

Angioedema: Angioedema of the face and/or larynx has been reported with GEMTESA. (5.2)

• The recommended dose is one 75 mg tablet orally once daily. (2.1)
• Swallow tablet whole with water. (2.1)
• Tablet may be crushed and mixed with applesauce. (2.1)

Tablets: 75 mg, oval, light green, film-coated, debossed with V75 on one side and no debossing on the other side.

The following adverse reactions have been identified during post-approval use of vibegron. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse events have been reported in association with vibegron use in worldwide postmarketing experience:

Urologic disorders: urinary retention

Skin and subcutaneous tissue disorders: angioedema of the face and larynx; hypersensitivity reactions, including urticaria, pruritus, rash and drug eruption; eczema

Gastrointestinal disorders: constipation

Pediatric use: Safety and effectiveness in pediatric patients have not been established. (8.4)

End-stage Renal Disease with or without Hemodialysis: Not recommended. (8.6)

Severe Hepatic Impairment: Not recommended. (8.7)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

GEMTESA^® is indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults.

The efficacy of GEMTESA was evaluated in a 12-week, double-blind, randomized, placebo-controlled, and active-controlled trial (Study 3003, NCT03492281) in patients with OAB (urge urinary incontinence, urgency, and urinary frequency). Patients were randomized 5:5:4 to receive either GEMTESA 75 mg, placebo, or active control orally, once daily for 12 weeks. For study entry, patients had to have symptoms of OAB for at least 3 months with an average of 8 or more micturitions per day and at least 1 urge urinary incontinence (UUI) per day, or an average of 8 or more micturitions per day and an average of at least 3 urgency episodes per day. Urge urinary incontinence was defined as leakage of urine of any amount because the patient felt an urge or need to urinate immediately. The study population included OAB medication-naïve patients as well as patients who had received prior therapy with OAB medications.

The co-primary endpoints were change from baseline in average daily number of micturitions and average daily number of UUI episodes at week 12. Additional endpoints included change from baseline in average daily number of “need to urinate immediately” (urgency) episodes and average volume voided per micturition.

A total of 1,515 patients received at least one daily dose of placebo (n=540), GEMTESA 75 mg (n=545), or an active control treatment (n=430). The majority of patients were White (78%) and female (85%) with a mean age of 60 (range 18 to 93) years.

Table 3 shows changes from baseline at week 12 for average daily number of micturitions, average daily number of UUI episodes, average daily number of “need to urinate immediately” (urgency) episodes, and average volume voided per micturition.

Figure 1 and Figure 2 show the mean change from baseline over time in average daily number of micturitions and mean change from baseline over time in average daily number of UUI episodes, respectively.

Figure 1: Mean (SE) Change from Baseline in the Average Daily Number of Micturitions

Figure 2: Mean (SE) Change from Baseline in the Average Daily Number of UUI Episodes in Patients with At Least 1 Average Daily UUI Episode at Baseline

Advise the patient to read the FDA-approved patient labeling (Patient Information).

GEMTESA 75 mg tablets are light green, oval, film-coated tablets, debossed with V75 on one side and no debossing on the other side.

GEMTESA is marketed in two packaging configurations:

Thirty (30) tablets in a HDPE bottle with a child-resistant cap, NDC 73336-075-30

Ninety (90) tablets in a HDPE bottle with a child-resistant cap, NDC 73336-075-90

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Keep this and all medications out of sight and reach of children.

Dispose unused medication via a take-back option if available; otherwise follow FDA instructions for disposal in the household trash. See www.fda.gov/drugdisposal for more information.

The safety, tolerability, and efficacy of GEMTESA was evaluated in a multinational 24-week, double-blind, randomized, placebo-controlled trial (Study 3005, NCT03902080) in male patients at least 45 years of age with OAB on pharmacological therapy (i.e., treatment with an alpha blocker, with or without a 5-alpha reductase inhibitor) for BPH. A total of 1105 patients were randomized 1:1 to receive either GEMTESA 75 mg or placebo once daily for 24 weeks. For study entry, patients had symptoms of OAB (an average of 8 or more micturitions per day, 3 or more urgency episodes per day with or without incontinence, and 2 or more nocturia episodes per night) while taking pharmacological therapy for at least 2 months for the treatment of lower urinary tract symptoms due to BPH. Randomization was stratified based on the baseline average number of micturition episodes per day, alpha blocker use with or without 5 alpha reductase inhibitor use, and urinary incontinence.

The co-primary endpoints were change from baseline in the average daily number of micturitions and the average daily number of “need to urinate immediately” (urgency) episodes at week 12. Additional endpoints included change from baseline in the average daily number of urge urinary incontinence (UUI) episodes and the average volume voided per micturition.

A total of 1104 patients received at least one daily dose of placebo (n=551) or GEMTESA 75 mg (n=553). The majority of patients were White (87%) and enrolled in the U.S. (56%). The mean age was 67 years (range 45 to 97) and at least 63% were ≥ 65 years.

Table 4 shows changes from baseline at week 12 for average daily number of micturitions, average daily number of urgency episodes, average daily number of UUI episodes and average volume voided per micturition.

Figure 3 and Figure 4 show the mean change from baseline over time in average daily number of micturitions and mean change from baseline over time in average daily number of urgency episodes, respectively.

Figure 3: Mean (SE) Change from Baseline in the Average Daily Number of Micturitions in Male Patients with BPH on Pharmacological Therapy

Figure 4: Mean (SE) Change from Baseline in the Average Daily Number of Urgency Episodes in Male Patients with BPH on Pharmacological Therapy

30 tablets

NDC 73336-075-30

Rx Only

GEMTESA^®

(vibegron) tablets

75 mg

One Tablet • Once Daily

May be swallowed whole or crushed

GEMTESA is indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adult males on pharmacological therapy for benign prostatic hyperplasia (BPH).

There is no experience with inadvertent GEMTESA overdosage. In case of suspected overdose, treatment should be symptomatic and supportive.

Vibegron is a selective beta-3 adrenergic agonist. The chemical name is (6S)-N-[4-[[(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl]methyl]phenyl]-4-oxo-7,8-dihydro-6H-pyrrolo[1,2-a]pyrimidine-6-carboxamide having a molecular formula of C₂₆H₂₈N₄O₃ and a molecular weight of 444.538 g/mol. The structural formula of vibegron is:

Vibegron is a crystalline, white to off-white to tan powder.

GEMTESA tablets, for oral administration contain 75 mg of vibegron and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, mannitol, and microcrystalline cellulose. The light green film coating contains FD&C Blue No. 2 - aluminum lake, hypromellose, iron oxide yellow, lactose monohydrate, titanium dioxide, and triacetin.

Angioedema of the face and/or larynx has been reported with GEMTESA. Angioedema has been reported to occur hours after the first dose or after multiple doses. Angioedema, associated with upper airway swelling, may be life-threatening. If involvement of the tongue, hypopharynx, or larynx occurs, immediately discontinue GEMTESA and provide appropriate therapy and/or measures necessary to ensure a patent airway. GEMTESA is contraindicated in patients with known hypersensitivity to vibegron or any component of GEMTESA [see Contraindications (4) and Adverse Reactions (6.2)].

The safety and effectiveness of GEMTESA in pediatric patients have not been established.

Of 526 patients who received GEMTESA in the clinical studies for OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency, 242 (46%) were 65 years of age or older, and 75 (14%) were 75 years of age or older [see Clinical Studies (14.1)]. No overall differences in safety or effectiveness of GEMTESA have been observed between patients 65 years of age and older and younger adult patients.

Of the total number of GEMTESA-treated patients in clinical studies for OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency in adult males on pharmacological therapy for benign prostatic hyperplasia (BPH), 347 (63%) were 65 years of age and older, while 100 (18%) were 75 years of age and older [see Clinical Studies (14.2)]. No overall differences in safety of GEMTESA have been observed between patients 65 years of age and older and younger adult patients.

GEMTESA is contraindicated in patients with known hypersensitivity to vibegron or any components of GEMTESA. Hypersensitivity reactions, such as angioedema, have occurred [see Warnings and Precautions (5.2) and Adverse Reactions (6.2)].

The following clinically significant adverse reaction is described elsewhere in the labeling:

• Urinary retention [see Warnings and Precautions (5.1)]

Concomitant use of GEMTESA increases digoxin maximal concentrations (C_max) and systemic exposure as assessed by area under the concentration-time curve (AUC) [see Clinical Pharmacology (12.3)]. Serum digoxin concentrations should be monitored before initiating and during therapy with GEMTESA and used for titration of the digoxin dose to obtain the desired clinical effect. Continue monitoring digoxin concentrations upon discontinuation of GEMTESA and adjust digoxin dose as needed.

No dosage adjustment for GEMTESA is recommended for patients with mild, moderate, or severe renal impairment (eGFR 15 to <90 mL/min/1.73 m²). GEMTESA has not been studied in patients with eGFR <15 mL/min/1.73 m² (with or without hemodialysis) and is not recommended in these patients [see Clinical Pharmacology (12.3)].

Vibegron's exposure-response relationship and the time course of pharmacodynamic response are not fully characterized.

Mean vibegron C_max and AUC increased in a greater than dose-proportional manner up to 600 mg (8 times the approved recommended dosage). Steady state concentrations are achieved within 7 days of once daily dosing. The mean accumulation ratio (R_ac) was 1.7 for C_max and 2.4 for AUC_0-24hr.

Urinary retention has been reported in patients taking GEMTESA. The risk of urinary retention may be increased in patients with bladder outlet obstruction and also in patients taking muscarinic antagonist medications for the treatment of OAB. Monitor patients for signs and symptoms of urinary retention, particularly in patients with bladder outlet obstruction or patients taking muscarinic antagonist medications for the treatment of OAB. Discontinue GEMTESA in patients who develop urinary retention [see Adverse Reactions (6.1)].

The recommended dosage of GEMTESA is one 75 mg tablet orally, once daily with or without food. Swallow GEMTESA tablets whole with a glass of water.

In adults, GEMTESA tablets also may be crushed, mixed with a tablespoon (approximately 15 mL) of applesauce and taken immediately with a glass of water [see Clinical Pharmacology (12.3)].

No dosage adjustment for GEMTESA is recommended for patients with mild to moderate hepatic impairment (Child-Pugh A and B). GEMTESA has not been studied in patients with severe hepatic impairment (Child-Pugh C) and is not recommended in this patient population [see Clinical Pharmacology (12.3)].

GEMTESA is a beta-3 adrenergic agonist indicated for the treatment of:

• overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults. (1.1)
• overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adult males on pharmacological therapy for benign prostatic hyperplasia (BPH). (1.2)

Vibegron is a selective human beta-3 adrenergic receptor agonist. Activation of the beta-3 adrenergic receptor increases bladder capacity by relaxing the detrusor smooth muscle during bladder filling.

Urinary Retention: Monitor for urinary retention, especially in patients with bladder outlet obstruction and also in patients taking muscarinic antagonist medications for OAB, in whom the risk of urinary retention may be greater. If urinary retention develops, discontinue GEMTESA. (5.1)

Angioedema: Angioedema of the face and/or larynx has been reported with GEMTESA. (5.2)

• The recommended dose is one 75 mg tablet orally once daily. (2.1)
• Swallow tablet whole with water. (2.1)
• Tablet may be crushed and mixed with applesauce. (2.1)

Tablets: 75 mg, oval, light green, film-coated, debossed with V75 on one side and no debossing on the other side.

The following adverse reactions have been identified during post-approval use of vibegron. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse events have been reported in association with vibegron use in worldwide postmarketing experience:

Urologic disorders: urinary retention

Skin and subcutaneous tissue disorders: angioedema of the face and larynx; hypersensitivity reactions, including urticaria, pruritus, rash and drug eruption; eczema

Gastrointestinal disorders: constipation

Pediatric use: Safety and effectiveness in pediatric patients have not been established. (8.4)

End-stage Renal Disease with or without Hemodialysis: Not recommended. (8.6)

Severe Hepatic Impairment: Not recommended. (8.7)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

GEMTESA^® is indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults.

The efficacy of GEMTESA was evaluated in a 12-week, double-blind, randomized, placebo-controlled, and active-controlled trial (Study 3003, NCT03492281) in patients with OAB (urge urinary incontinence, urgency, and urinary frequency). Patients were randomized 5:5:4 to receive either GEMTESA 75 mg, placebo, or active control orally, once daily for 12 weeks. For study entry, patients had to have symptoms of OAB for at least 3 months with an average of 8 or more micturitions per day and at least 1 urge urinary incontinence (UUI) per day, or an average of 8 or more micturitions per day and an average of at least 3 urgency episodes per day. Urge urinary incontinence was defined as leakage of urine of any amount because the patient felt an urge or need to urinate immediately. The study population included OAB medication-naïve patients as well as patients who had received prior therapy with OAB medications.

The co-primary endpoints were change from baseline in average daily number of micturitions and average daily number of UUI episodes at week 12. Additional endpoints included change from baseline in average daily number of “need to urinate immediately” (urgency) episodes and average volume voided per micturition.

A total of 1,515 patients received at least one daily dose of placebo (n=540), GEMTESA 75 mg (n=545), or an active control treatment (n=430). The majority of patients were White (78%) and female (85%) with a mean age of 60 (range 18 to 93) years.

Table 3 shows changes from baseline at week 12 for average daily number of micturitions, average daily number of UUI episodes, average daily number of “need to urinate immediately” (urgency) episodes, and average volume voided per micturition.

Figure 1 and Figure 2 show the mean change from baseline over time in average daily number of micturitions and mean change from baseline over time in average daily number of UUI episodes, respectively.

Figure 1: Mean (SE) Change from Baseline in the Average Daily Number of Micturitions

Figure 2: Mean (SE) Change from Baseline in the Average Daily Number of UUI Episodes in Patients with At Least 1 Average Daily UUI Episode at Baseline

Advise the patient to read the FDA-approved patient labeling (Patient Information).

GEMTESA 75 mg tablets are light green, oval, film-coated tablets, debossed with V75 on one side and no debossing on the other side.

GEMTESA is marketed in two packaging configurations:

Thirty (30) tablets in a HDPE bottle with a child-resistant cap, NDC 73336-075-30

Ninety (90) tablets in a HDPE bottle with a child-resistant cap, NDC 73336-075-90

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Keep this and all medications out of sight and reach of children.

Dispose unused medication via a take-back option if available; otherwise follow FDA instructions for disposal in the household trash. See www.fda.gov/drugdisposal for more information.

The safety, tolerability, and efficacy of GEMTESA was evaluated in a multinational 24-week, double-blind, randomized, placebo-controlled trial (Study 3005, NCT03902080) in male patients at least 45 years of age with OAB on pharmacological therapy (i.e., treatment with an alpha blocker, with or without a 5-alpha reductase inhibitor) for BPH. A total of 1105 patients were randomized 1:1 to receive either GEMTESA 75 mg or placebo once daily for 24 weeks. For study entry, patients had symptoms of OAB (an average of 8 or more micturitions per day, 3 or more urgency episodes per day with or without incontinence, and 2 or more nocturia episodes per night) while taking pharmacological therapy for at least 2 months for the treatment of lower urinary tract symptoms due to BPH. Randomization was stratified based on the baseline average number of micturition episodes per day, alpha blocker use with or without 5 alpha reductase inhibitor use, and urinary incontinence.

The co-primary endpoints were change from baseline in the average daily number of micturitions and the average daily number of “need to urinate immediately” (urgency) episodes at week 12. Additional endpoints included change from baseline in the average daily number of urge urinary incontinence (UUI) episodes and the average volume voided per micturition.

A total of 1104 patients received at least one daily dose of placebo (n=551) or GEMTESA 75 mg (n=553). The majority of patients were White (87%) and enrolled in the U.S. (56%). The mean age was 67 years (range 45 to 97) and at least 63% were ≥ 65 years.

Table 4 shows changes from baseline at week 12 for average daily number of micturitions, average daily number of urgency episodes, average daily number of UUI episodes and average volume voided per micturition.

Figure 3 and Figure 4 show the mean change from baseline over time in average daily number of micturitions and mean change from baseline over time in average daily number of urgency episodes, respectively.

Figure 3: Mean (SE) Change from Baseline in the Average Daily Number of Micturitions in Male Patients with BPH on Pharmacological Therapy

Figure 4: Mean (SE) Change from Baseline in the Average Daily Number of Urgency Episodes in Male Patients with BPH on Pharmacological Therapy

30 tablets

NDC 73336-075-30

Rx Only

GEMTESA^®

(vibegron) tablets

75 mg

One Tablet • Once Daily

May be swallowed whole or crushed