Materia Medica
Gemtesa® (vibegron) Habibur Rahman, PharmD Courtney Simpkins, PharmD Intro Gemtesa® (vibegron) is a novel β3-adrenergic receptor (β3-AR) agonist that is FDA approved for treatment of overactive bladder (OAB) with symptoms of urge incontinence, urgency, and urinary frequency.1 It is the first selective β3-AR agonist to achieve FDA approval since introduction of mirabegron in 2012, the only other β3-AR agonist on the market. Gemtesa® is highly selective, with a greater than 9000-fold selectivity for the β3-AR compared to β1 or β2 receptors. The selectivity of this agent is a point of emphasis as broad β receptor agonism can lead to greater adverse drug reactions. Other OAB medications target muscarinic receptors and have significant anticholinergic effects.2
Safety In a 2018 phase 3 trial conducted in patients of Japanese descent with OAB, the incidence of drug-related adverse events associated with Gemtesa® was similar to placebo and less than the comparator anticholinergic, imidafenacin.3 In this four-arm, parallel-group, 12-week active treatment, placebo-controlled trial, patients with OAB symptoms for greater than or equal to 6 months
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were randomized to receive Gemtesa® 50mg daily (n=370), Gemtesa® 100mg daily (n=369), placebo (n=369), or imidafenacin 0.1mg twice daily (n=117) in a 3.3:3.3:3.3:1 ratio respectively. Safety was assessed based on rates of adverse events, clinical testing, postvoid residuals, vitals, and 12-lead electrocardiogram (ECG). Clinical tests included hematological markers, biochemical markers, and urinalysis. Treatment-emergent adverse events (TEAE) were all adverse events recorded after the start of each treatment that may or may not be attributed to each treatment arm. From a safety standpoint, the most common TEAE was nasopharyngitis (8.6%, 9.5%, 7.3%, 3.4%), cystitis (2.4%, 2.2%, 0.8%, 0.9%), and blood alkaline phosphatase increases (0%, 0.3%, 0.3%, 2.6%) for the 50mg, 100mg, placebo, and imidafenacin treatment arms respectively. Drug-related TEAE were adverse events that occurring during treatment that investigators attributed to each treatment arm. The most common drug related TEAE were blood alkaline phosphatase increase (0%, 0.3%, 0.3%, 1.7%) and hypertension (0%, 0%, 0%, 1.7%). Serious TEAE included back pain, pyelonephritis, colon cancer, acute myeloid leukemia, dizziness, and breast cancer. These occurred in 1 patient in each active drug treatment
arm and in 3 patients in the placebo arm, none of which were thought to be related to the intervention. TEAEs that led to discontinuation were in 3 patients in the 50mg Gemtesa® group (edema, eczema, and neutrophil count decrease), and 3 patients in the 100mg Gemtesa® group (supraventricular tachycardia, blood creatinine increase, and abdominal pain). There were no other notable changes in clinical laboratory values and vital signs than the ones mentioned. There were similar rates of ECG changes among all groups as well as no substantial changes in postvoid residuals. This study demonstrated the relative safety of Gemtesa® with low incidences of key safety parameters. In a phase 3 trial, patients with OAB were treated with Gemtesa® 50mg (n=116) or 100mg (n=51), and the long-term safety profile of the medication was evaluated.4 In patients that did not respond appropriately within 8 weeks to 50mg, they were increased to 100mg and continued this treatment for 44 weeks. The primary safety outcome was evaluated in overall percentages of TEAE which were 55.1% and 16.2% for 50mg and 100mg respectively. Three cases of cystitis and 5 cases of postvoid residual increase were discovered, all in the 50mg group and none in the 100mg group. Severe TEAE, which were angina pectoris (n=1), falls (n=1),
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