It was globally approved on September 21, 2018, in Japan for OAB.Vibegron has been proven effective in 5 key clinical trials.A phase IIb global trial completed in 2013 of 1395 patients, of which 89.7% were women and 63.3% had not been treated previously, demonstrated a significant decrease in daily micturitions and urgent urinary incontinence episodes upon administration of vibegron.An international phase III trial of 506 participants completed in 2019 found statistically significant efficacy of vibegron after 2 weeks of daily administration. The adverse effect rates in patients treated with vibegron were comparable to those in patients who received a placebo.GEMTESA, a drug using vibegron as an active ingredient was approved by the FDA on December 23, 2020, after an additional phase III international trial of 1085 patients. Society and culture
Legal status
Vibegron was approved for medical use in the United States in December 2020. Names
Vibegron is the international nonproprietary name (INN). Mechanism of action
Vibegron is a selective agonist for the beta-3 adrenergic receptor (β3-AR). The receptors are located in the kidneys, urinary tract and bladder tissue. Upon binding, the β3 receptor undergoes a conformational change. This induces the activation of adenylate cyclases via G proteins and thereby promotes the formation of cyclic adenosine monophosphate (cAMP). The consequence of this cascade is an increased intracellular cAMP concentration which triggers activation of cAMP-dependent protein kinase A and causes a reduction of Ca2+ concentration in the cytoplasm. The kinase then phosphorylates myosin chains and thereby inhibits muscle contraction.The final effect of vibegron is muscle relaxation in the bladder.
These outcomes concluded that there was a reduction in urgency to urinate, a decrease in micturitions and a decrease in average volume voided per micturition. There is also an improvement observed of the symptoms when Vibegron is administered over a longer period (52 weeks) concluding that it is effective and safe for longer use. In severe patients, increasing the dose was accompanied by similar beneficial effects when there was first a lack of these. Quality of life of the patients is improved, including a reduction of nocturia. Adverse effects
The most common side effects of Vibegron are a dry mouth, constipation, headache, nasopharyngitis, diarrhea, nausea, bronchitis, urinary tract infection and upper respiratory tract infection. An indication is made that upon urinary retention development, the patient should stop using the drug. Risk assessment for the drug in pregnant women has yet to be evaluated. Interactions
Vibegron is in contrast to other OAB drugs very selective and leads to a lesser degree in unwanted side effects. Vibegron is found to be a substrate for CYP3A4 in vivo, but does not actually induce or inhibit any of the cytochrome P450 enzymes and is thus less likely to take part in drug–drug interactions (DDI). Here vibegron differs from the previous overactive bladder drug mirabegron, which was known to be associated in various drug–drug interactions by inhibiting CYP2D6 or inducing CYP3A4, CYP2D6 and CYP2C9 in the liver.Using Vibegron only (monotherapy) has positive effects on OAB and UUI, but a combination with other drugs can have additional effects.