Obesity Advocates Challenge FDA Over Drug Approval Process Disparities

Prescription bottle and pills | Image credit: Andy Dean - stock.adobe.com

In a joint statement, organizations in the obesity and metabolic health fields urged the FDA to address critical gaps in the testing and approval process for drugs intended for use by individuals with obesity. The American Society for Metabolic and Bariatric Surgery, the Obesity Action Coalition (OAC), the Obesity Medicine Association (OMA), the STOP Obesity Alliance, and The Obesity Society (TOS) are collectively urging regulatory action to ensure the safety and efficacy of medications for the 42% of the US population affected by obesity.

At the core of the appeal is the current lack of a requirement for new drugs to undergo specific testing in people with obesity before approval. The exclusion criteria in clinical trials also regularly bar individuals with higher body weights from participation. According to the statement, this oversight can have serious consequences, as drug kinetics may significantly differ in larger bodies, rendering general population dosing instructions that are potentially unsafe and ineffective for those with obesity.

The organizations stressed that people with obesity, who represent a substantial portion of the population, are being exposed to unnecessary risks of adverse events, including death, due to this practice. This is in stark contrast to drug testing policies for other sub-populations, such as those with renal or liver impairment, and for pediatric patients.

“Drug companies have an interest in reducing inter-subject variability, because in narrower subsections, drugs are more likely to perform as expected, thereby increasing the odds of getting approved,” Jamy Ard, MD, FTOS, president-elect of TOS, said in the statement. “Unfortunately, variation in body size is easy to identify and as a result, drug companies often structure clinical trials to exclude people with obesity.”

The call for action was accompanied by a demand for drug companies that are marketing medications with known safety or effectiveness issues at standard doses for people with obesity to immediately update their labeling with correct usage instructions for this demographic. The statement coincided with a special issue of the Journal of Clinical Pharmacology, published by the American College of Clinical Pharmacology, addressing the necessity of studying people with obesity in the drug development process. This initiative originated from an FDA workshop on drug efficacy and safety in people with obesity held in November 2022.

“People with obesity deserve to know if the drugs they use are safe and effective for them—and so do their doctors,” Joe Nadglowski, president and CEO of OAC, stated. “These drugs are used every day by people who don’t know they might not be effective, and include treatments for depression, schizophrenia, emergency contraception, preventing organ transplant rejection, infections, and cancer.”

Experts argued that failure to account for the unique needs of individuals with obesity can have severe consequences. For example, certain drugs like brexpiprazole (Rexulti), used to treat schizophrenia and depression, have been shown to take significantly longer to reach effective levels in people with obesity. The delayed response can lead to underdosing, potentially placing patients at risk of harming themselves or others.

Additionally, the increased half-life of drugs in people with obesity can lead to inadvertent drug-drug interactions, as seen in the case of posaconazole (Noxafil), an antifungal with a longer half-life in patients with obesity. The lack of specific testing in this population poses risks of prolonged drug interactions, which current labeling fails to address.

The organizations called on Congress and the FDA to mandate drug companies to test new drugs on relevant subsections of the population, emphasizing the importance of ensuring the safety and efficacy of medications for people with obesity. They argued that this failure to address the needs of individuals with obesity not only poses harm, but also reduces trust in the health care system. As one patient expressed in the statement, "You're either invisible, or the answer is to lose weight, even with mental health."

“We must ensure drugs are safe and effective and labeled correctly for everyone for whom they are intended,” Angela Fitch, MD, FACP, FOMA, president of the OMA, stated. “Drug companies don’t get a pass on people with obesity.”

Reference

Joint statement in support of closing gaps in the drug approval process and drug labeling for people with obesity. News release. Obesity Action Coalition. Published November 28, 2023. Accessed December 4, 2023. https://www.obesityaction.org/statement-drug-approval-labeling/