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Men pharmacologically treated for benign prostatic hyperplasia (BPH) experienced significant improvements in overactive bladder (OAB) symptoms after treatment with vibegron (Gemtesa), according to results from a .

After 12 weeks of treatment, vibegron recipients experienced significant reductions in average daily micturition episodes (-2.04 with vibegron vs -1.30 with placebo, P<0.0001) and average daily urgency episodes (-2.88 vs -1.93 respectively, P<0.0001), thus meeting the COURAGE trial's co-primary endpoints, reported Janet Owens-Grillo, PhD, MS, of Sumitomo Pharma America, and colleagues.

"This suggests that vibegron is similarly efficacious at reducing OAB symptoms in patients with and without coexisting BPH and may work additively with pharmacologic BPH treatment consisting of α-blockers with or without 5α-reductase inhibitors," the authors wrote in the .

They noted that vibegron showed efficacy as early as week 2 and maintained it through week 24 in COURAGE. Additionally, they said, vibegron was generally safe and well tolerated given that adverse event (AE) rates were similar between treatment and placebo groups.

These results were broadly consistent with those from the that had established vibegron's efficacy and safety in a phase III study in overactive bladder. That study led to vibegron being FDA approved to treat OAB with symptoms of urinary frequency, urgency, and urge urinary incontinence (UUI).

The question in COURAGE was whether this selective β3-adrenergic receptor agonist would improve OAB symptoms in men undergoing treatment for BPH.

In addition to meeting the study's primary endpoints, Owens-Grillo and colleagues reported that participants receiving vibegron were more likely to experience both ≥50% and ≥75% reductions in urgency episodes at all time points compared with placebo -- these ≥50% and ≥75% thresholds having been associated with clinical meaningfulness, based on the prior literature.

Vibegron was also associated with a significant reduction in mean daily nocturia episodes (-0.88 vs -0.66, P=0.002), UUI episodes (-2.19 vs -1.39, P=0.003), International Prostate Symptom Score-storage scores (-3.0 vs -2.1, P<0.0001), and volume voided per micturition (25.63 mL vs 10.56 mL, P<0.0001).

The demonstrated reduction in nocturnal frequency was highlighted as "lending credence to the importance of storage symptoms as a contributor to nocturnal urinary events," according to Roger Dmochowski, MD, MMHC, of Vanderbilt University Medical Center in Nashville, Tennessee.

"Mixed urinary symptomatology arising from outlet obstruction with associated bladder over-activity occurs in substantial numbers of men in the at-risk age groups for benign prostatic destruction," he wrote in an accompanying .

"Storage dysfunction, however, may present in men without discernible outlet concerns, and therefore critical emphasis is placed on the clinician to differentiate symptom etiology (obstructive, irritative, or mixed) prior to definitive intervention to assure patient awareness and adequate informed consent as to risk of persistent storage symptoms after surgical intervention for the outlet (if indicated)," Dmochowski stressed.

The COURAGE trial was conducted at 82 sites in North America and Europe. Eligible participants were men ≥45 years of age with persistent OAB symptoms (≥8 micturitions and ≥3 urgency episodes per day) for ≥2 months, and previously diagnosed BPH treated with a stable dose of an α-blocker with or without a 5α-reductase inhibitor.

Out of 1,105 men who were randomized, 1,104 received ≥1 dose of study medication and 87.3% completed the trial. The full analysis set included 1,080 participants (538 randomized to vibregon and 542 to placebo).

The mean age of the study cohort was 67 years. The majority were white (87.6%) and from the U.S. (56%).

About two-thirds of patients had pre-existing hypertension and one-quarter had incontinence at baseline. The mean number of daily micturitions at baseline was 11.3 and 11.7 in the vibegron and placebo groups, and the mean number of daily urgency episodes was 9.0 and 9.3 in the two groups, respectively.

Regarding safety, 45.0% and 39.0% of patients receiving vibegron and placebo, respectively, experienced at least one treatment-emergent adverse event (TEAE). Among the most frequent ones were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), urinary tract infection (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%). TEAEs leading to study discontinuation occurred in 2.9% of patients in the vibegron group and 2.7% in the placebo group.

Serious adverse events (AEs) occurred in 4.3% and 2.9% of patients receiving vibegron and placebo, respectively, with no serious AEs considered to be treatment-related by the COURAGE authors.

In the vibegron group, six participants were diagnosed with five distinct neoplasms including basal cell carcinoma in two patients; and one patient each developing pancreatic adenocarcinoma, adenocarcinoma of the colon with metastatic hepatic mass, metastatic renal cell carcinoma, and plasma call myeloma. In the placebo group, one patient was diagnosed with bladder transitional cell carcinoma.

All neoplasms were diagnosed within 80 days of starting the study and none were considered treatment-related by investigators.

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