In recent years, regulators including FDA have increased their focus on the potential of drugs to cause blood pressure increases. To that end, the agency asked Urovant (Irvine, California) to study the impact of the beta-3 adrenergic receptor agonist vibegron on blood pressure.
The study, recently published in the Journal of Urology, found no significant change in blood pressure among either vibegron or placebo recipients. There were 96 patients in the vibegron group. Another 101 received placebo. “The good news was that the changes in blood pressure were trivial — on average less than one millimeter of mercury,” said Dr. Michael A. Weber, a professor of medicine at SUNY Downstate College of Medicine in New York, who was involved in the study.
Weber recently summarized the results at the Annual Meeting of the American Urological Association.
FDA approved vibegron in late 2020. In addition, the agency approved another beta-3 adrenergic receptor agonist known as mirabegron from Astellas Pharma in 2012. “There was some concern with early studies of mirabegron that it might be raising blood pressure,” said Weber. The reason being is that beta receptors are found in the heart and blood vessels and could potentially influence blood pressure.
But vibegron, along with mirabegron, are beta-3 drugs. So while beta-1 and beta-2 drugs could affect blood pressure, beta-3 drugs are “probably going to be neutral,” Weber reasoned.
While the label for mirabegron mentions the possible increase in blood pressure, “it’s turned out not to be very much of a problem,” Weber said.
But when vibegron came along, the agency recommended doing “a careful clinical trial to show you don’t have an adverse blood pressure effect,” Weber continued.
The trial measured ambulatory blood pressure multiple times per hour throughout the day. “If you just simply average them out, you get a very strong representative value for a patient’s whole-day blood pressure,” Weber said. “The FDA loves that because, now, you can look at a new drug and quantify very precisely whether there was a change.”
The researchers also crawled through the data to see if any individual patients appeared to have dangerous changes in blood pressure over the four-week trial period. Again, they could not find outliers compared with just placebo recipients. “It was a second reassurance that everything was okay,” Weber said.