Herpes simplex virus gene therapy for dystrophic epidermolysis bullosa (DEB).

The FDA has recently approved Krystal biotech's beremagene geperpavec (B-VEC, Vyjuvek) to treat the wounds of dystrophic epidermolysis bullosa (DEB) patients. This represents a giant step, not only toward the treatment of this devastating disease, but also for the whole field of non-replicative (nr) recombinant HSV-1 vectors for gene therapy. To view this Bench to Bedside, open or download the PDF.

Treatment of neurogenic detrusor overactivity and overactive bladder with Botox (onabotulinumtoxinA): Development, insights, and impact.

Neurogenic detrusor overactivity (NDO) is a complication of multiple sclerosis, spinal cord injury (SCI), stroke, head injury, and other conditions characterized by damage to the upper motor neuronal system. NDO often leads to high bladder pressure that may cause upper urinary tract damage and urinary incontinence (UI). Prior to the use of onabotulinumtoxinA, oral anticholinergics and surgical augmentation cystoplasty were the treatment options.

Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder.

Background: Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective β-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence.

Efficacy and Safety of Vibegron for the Treatment of Overactive Bladder in Women: A Subgroup Analysis From the Double-Blind, Randomized, Controlled EMPOWUR Trial.

Importance: The international phase 3 EMPOWUR trial demonstrated efficacy and safety of vibegron, a newer β 3 -adrenergic receptor agonist, in adults with overactive bladder (OAB). Women are disproportionately affected by OAB, especially those with bothersome symptoms, such as urge urinary incontinence (UUI).

Objective: This subgroup analysis from EMPOWUR assessed efficacy and safety of vibegron in women.

Pharmacokinetics and Safety of Vibegron 75 mg Administered as an Intact or Crushed Tablet in Healthy Adults.

Oral pharmacotherapy for overactive bladder, a condition that increases with age, includes anticholinergics and β -adrenergic receptor agonists. Older adults, including those with dysphagia, may have difficulty swallowing tablets. In this phase 1 study in healthy adults, we assessed the pharmacokinetic profile of the β -adrenergic receptor agonist vibegron administered as a single 75-mg dose as an intact tablet versus crushed and mixed with applesauce.

Efficacy and safety of vibegron for the treatment of irritable bowel syndrome in women: Results of a randomized, double-blind, placebo-controlled phase 2 trial.

Background: Preclinical and clinical studies suggest that β -adrenergic receptor activation may be a novel target for treating abdominal pain and gastrointestinal motility dysfunction in patients with irritable bowel syndrome (IBS). This proof-of-concept study evaluated the efficacy and safety of the β -adrenergic agonist vibegron in treating IBS-related pain.

Methods: Adult women with predominant-diarrhea IBS (IBS-D) or with mixed diarrhea/constipation (IBS-M), diagnosed using Rome IV criteria, were randomized 1:1 to receive once-daily vibegron 75 mg or placebo for 12 weeks.

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

Pharmacologic treatment for overactive bladder (OAB), which is characterized by bothersome symptoms such as urgency and urge urinary incontinence (UUI), includes anticholinergics and β-adrenergic receptor agonists. Anticholinergics are associated with adverse effects including dry mouth, constipation, cognitive impairment, and increased risk of dementia. Therefore, the drug class of β-adrenergic receptor agonists may represent an effective, safe treatment option.

Effects of vibegron on ambulatory blood pressure in patients with overactive bladder: results from a double-blind, placebo-controlled trial.

Objectives: To characterize the blood pressure (BP) profile of the new β3-adrenergic receptor agonist, vibegron, in patients with overactive bladder.

Methods: Patients were randomized to once-daily vibegron 75 mg or placebo for 28 days and underwent ambulatory BP monitoring. The primary endpoint was change from baseline (CFB) to day 28 in mean daytime ambulatory systolic BP (SBP).

OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial.

Purpose: Overactive bladder affects 12% to 17% of the general population and almost a third experience urinary incontinence, which may severely impact health related quality of life. Oral anticholinergics are the mainstay of pharmacological treatment but they are limited by inadequate efficacy or side effects, leading to a high discontinuation rate. We report the results of the first large (557 patients), phase 3, placebo controlled trial of onabotulinumtoxinA in patients with overactive bladder and urinary incontinence inadequately managed with anticholinergics.

A multicenter, randomized, double-blind, placebo controlled study of onabotulinumtoxinA 200 U to treat lower urinary tract symptoms in men with benign prostatic hyperplasia.

Purpose: We assessed the efficacy and tolerability of onabotulinumtoxinA 200 U vs placebo to treat lower urinary tract symptoms/benign prostatic hyperplasia in men previously treated with oral benign prostatic hyperplasia medication in a 24-week phase 2, multicenter, double-blind, randomized, placebo controlled, parallel group trial.

Materials And Methods: Patients with I-PSS (International Prostate Symptom Score) 14 or greater, peak urinary flow rate 4 to 15 ml per second and total prostate volume 30 to 80 ml were randomized 1:1 to a single intraprostatic treatment of onabotulinumtoxinA 200 U or placebo. A single-blind sham procedure followed by a 4-week run-in was included to attempt to minimize any potential placebo effect.

OnabotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity [corrected] regardless of concomitant anticholinergic use or neurologic etiology.

Introduction: To evaluate the efficacy and safety of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity (NDO) in subpopulations of etiology (multiple sclerosis [MS] or spinal cord injury [SCI]) and concomitant anticholinergics (use/non-use).

Methods: Data were pooled from two double-blind, placebo-controlled, pivotal, phase 3 studies including a total of 691 patients with ≥ 14 urinary incontinence (UI) episodes/week due to MS (n = 381) or SCI (n = 310). Patients received intradetrusor injections of onabotulinumtoxinA 200U (n = 227), 300U (n = 223), or placebo (n = 241).

OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial.

Background: Overactive bladder (OAB) syndrome with urinary incontinence (UI) is prevalent in the population and impairs health-related quality of life (HRQOL).

Objective: To assess the impact on efficacy, safety, and HRQOL of onabotulinumtoxinA (BOTOX(®), Allergan, Inc.) treatment in patients with OAB with UI.

OnabotulinumtoxinA improves urodynamic outcomes in patients with neurogenic detrusor overactivity.

Aims: To evaluate the effect of onabotulinumtoxinA on urodynamic outcomes in patients with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).

Methods: Results from two pivotal Phase III trials (n = 691) were pooled. MS or SCI patients with NDO, received intradetrusor onabotulinumtoxinA 200 U (n = 227), 300 U (n = 223), or placebo (n = 241).

Long-term efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: an interim analysis.

Objective: To evaluate the long-term efficacy and safety of repeat onabotulinumtoxinA injections in patients inadequately managed by anticholinergics for urinary incontinence (UI) due to neurogenic detrusor overactivity.

Materials And Methods: Patients who completed either of 2 preceding phase III studies were offered entry into an extension study and received repeat onabotulinumtoxinA 200 U or 300 U. The data were integrated across the phase III and ongoing extension studies.

OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial.

Purpose: Overactive bladder affects 12% to 17% of the general population and almost a third experience urinary incontinence, which may severely impact health related quality of life. Oral anticholinergics are the mainstay of pharmacological treatment but they are limited by inadequate efficacy or side effects, leading to a high discontinuation rate. We report the results of the first large (557 patients), phase 3, placebo controlled trial of onabotulinumtoxinA in patients with overactive bladder and urinary incontinence inadequately managed with anticholinergics.

A randomized double-blind placebo-controlled phase 2 dose-ranging study of onabotulinumtoxinA in men with benign prostatic hyperplasia.

Background: Botulinum toxin treatment has been investigated as a minimally invasive alternative to oral medications in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (LUTS/BPH).

Objective: To explore the efficacy of onabotulinumtoxinA 100 U, 200 U, and 300 U versus placebo in men with LUTS/BPH in a phase 2 dose-ranging study.

Design, Setting, And Participants: A multicenter double-blind randomized, placebo-controlled 72-wk study enrolled men ≥ 50 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) ≥ 12, total prostate volume (TPV) 30-100ml, and maximum flow rate (Q(max)) 5-15 ml/s.

Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity.

Purpose: We assessed the efficacy, safety and effects on quality of life of onabotulinumtoxinA in patients with neurogenic detrusor overactivity.

Materials And Methods: In this 52-week, international, multicenter, double-blind, randomized, placebo controlled trial 416 patients with neurogenic detrusor overactivity and urinary incontinence (14 or more episodes per week) resulting from multiple sclerosis (227) and spinal cord injury (189) were treated with intradetrusor injections of onabotulinumtoxinA (200 or 300 U) or placebo. The primary end point was the change from baseline in the mean number of urinary incontinence episodes per week at week 6.

Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial.

Background: Neurogenic detrusor overactivity (NDO) frequently results in urinary incontinence (UI) which impairs quality of life (QOL) and puts the upper urinary tract at risk.

Objective: To assess the effects of onabotulinumtoxinA (BOTOX(®), Allergan, Inc.) on UI, urodynamic variables, and QOL in incontinent patients with NDO.

Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxinA in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder.

Aims: We assessed the effects of onabotulinumtoxinA (BOTOX®) on clinical and urodynamic variables in patients with idiopathic overactive bladder (OAB) and urinary urgency incontinence (UUI) with or without detrusor overactivity (DO), inadequately managed with anticholinergics.

Methods: Three hundred thirteen patients with OAB were randomized to double-blind intradetrusor injection with placebo (n = 44) or 1 of 5 onabotulinumtoxinA doses (50-300 U; n = 269). Primary efficacy variable was change from baseline in UUI episodes/week at week 12.

Efficacy and safety of onabotulinumtoxinA for idiopathic overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial.

Purpose: Treatment options for patients with overactive bladder refractory to anticholinergics are limited. We assessed the dose response across a range of doses of onabotulinumtoxinA (BOTOX®) in patients with idiopathic overactive bladder and urinary urgency incontinence whose symptoms were not adequately managed with anticholinergics.

Materials And Methods: In a phase 2, multicenter, randomized, double-blind study, 313 patients with idiopathic overactive bladder and urinary urgency incontinence experiencing 8 or more urinary urgency incontinence episodes a week and 8 or more micturitions daily at baseline received 50, 100, 150, 200 or 300 U intradetrusor onabotulinumtoxinA, or placebo.

Epidemiology and healthcare utilization of neurogenic bladder patients in a US claims database.

Aims: To characterize the patient profile, medication utilization, and healthcare encounters of patients with neurogenic bladder dysfunction related to incontinence.

Methods: Medical and pharmacy claims were retrospectively analyzed from April 1, 2002 to March 31, 2007 to characterize neurogenic bladder patients. There were 46,271 patients in the Neurogenic bladder cohort, and 9,315 and 4,168 patients in Multiple Sclerosis (MS) and Spinal Cord Injury (SCI) subcohorts, respectively.

Efficacy, safety and tolerability of fesoterodine for overactive bladder syndrome.

Purpose: We evaluated the efficacy, tolerability and safety of the new antimuscarinic agent fesoterodine relative to placebo for overactive bladder syndrome.

Materials And Methods: This was a randomized, double-blind, placebo controlled, multicenter trial performed in the United States. Overall 836 subjects with urinary frequency, urinary urgency or urgency urinary incontinence were randomized to placebo (274), 4 mg fesoterodine (283) or 8 mg fesoterodine (279) once daily for 12 weeks.

Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder.

Objective: To determine the efficacy, tolerability, and safety of fesoterodine in subjects with overactive bladder (OAB).

Methods: This was a multicentre, randomised, double-blind, placebo- and active-controlled trial with tolterodine extended release (ER) to assess the efficacy and safety of fesoterodine. Eligible subjects (> or =18 yr) with increased micturition frequency and urgency and/or urgency urinary incontinence (UUI) were randomised to placebo, fesoterodine 4 mg, fesoterodine 8 mg, or tolterodine ER 4 mg for 12 wk.