The Test

The Failure to Test Drugs in People with Obesity

Scientists and regulators at the FDA have identified a critical gap in new drug development and labeling. It is the failure to test new drugs in people with obesity. Where there are differences in clinical responses and safety, labeling – the instructions for safe use – should reflect those differences. But in many cases, they do not.

In November, FDA and the University of Maryland convened a workshop to discuss this issue. FDA Commissioner Robert Califf opened the workshop, observing that persons with obesity are often excluded from clinical trials for new drugs:

“This may be in part because there are generally no FDA regulatory requirements at present to
evaluate weight as a specific issue. Consequently, they continue to be underrepresented in research and in clinical trials, making it difficult to obtain the necessary data to inform dosing of a newly marketed drug in individuals with obesity.”

A Gap in Representation

The lead physician in FDA’s Division of Diabetes, Lipid Disorders, and Obesity is Laura Higginbotham. She noted that excluding people with obesity from clinical test programs for new drugs is a clear problem, saying:

“Subjects who are enrolled in our clinical trials should be reflective of those who are intended to use the drug once it’s approved. And if patients with obesity are not being enrolled in our clinical trials, I see that as a major generalizability issue.”

The Case of Brexpiprazole

A case in point would be brexpiprazole – an important drug sold as Rexulti for schizophrenia and major depression. The clinical trials that provided the basis for approval excluded patients with a BMI greater than 35. So the directions for use (FDA-approved labeling) are based on a skewed patient population.

This is an important problem for two reasons. First, we know that obesity is common in persons with schizophrenia. In fact, a study from researchers in Yale’s Department of Psychiatry tells us that the prevalence may be in the range of 60 percent.

Second, we know that people with obesity require a different dosing regimen for safe and effective use of brexpiprazole. Without adjusting the dosing regimen for people with obesity, most of them will not achieve safe and therapeutic drug levels. But the directions for use of brexpiprazole omit this information.

Assuring Safety and Efficacy in Persons with Obesity

Persons with obesity will soon represent half of the U.S. population. Brexpiprazole is but one example of many drugs that are not adequately labeled for safe and effective use in these people.

We have the knowledge. It’s time for FDA and Pharma to act on it. Update current labels. Require adequate representation in clinical trials for future drugs.

Click here for all of the slides and presentations from the workshop sponsored by FDA and the University of Maryland. For further perspective, click here, here, and here.

The Test, photograph by Lena Gulenko, licensed under CC BY 4.0

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March 29, 2023

One Response to “The Failure to Test Drugs in People with Obesity”

  1. March 29, 2023 at 8:47 am, Allen Browne said:

    Duh! Pharmacokinetics 101!