The Obesity Action Coalition (OAC) announces the publication of a ‘Joint statement in support of closing gaps in the drug approval process and drug labeling for people with obesity’. The statement is co-signed by the OAC, The Obesity Society, the Stop Obesity Alliance, the Obesity Medicine Association, and the American Society for Metabolic and Bariatric Surgery - the leading scientific, medical and patient advocacy organisations in support of people with obesity.
“We must ensure drugs are safe and effective and labelled correctly for everyone for whom they are intended,” said Dr Angela Fitch, President of the OMA, the largest organization of physicians, nurse practitioners, physician assistants, and other health care providers working every day to improve the lives of patients affected by obesity. “Drug companies don’t get a pass on people with obesity.”
The statement calls for the FDA to close gaps in the testing and approval process for drugs intended for use by people with obesity for conditions other than obesity. The statement also urges drug companies that are currently marketing drugs that have issues with safety or effectiveness for people with obesity to update their labelling immediately to provide appropriate usage instructions.
"Proceedings of a workshop organized in part by FDA scientists dealing with this subject were published this month, which tells us that FDA is fully aware of this issue. Everyone deserves to know the drugs they use are safe and effective. The FDA and drug companies need to take action now," explained Joe Nadglowski, President and CEO of the OAC. “People with obesity deserve to know if the drugs they use are safe and effective for them - and so do their doctors. 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.”
People with obesity make up 42% of the US population, yet there is no requirement that new prescription drugs be shown to be safe and effective for people with obesity before FDA approves them. This means that every day, people with obesity are using FDA-approved drugs without full assurance that they are safe and effective for them.
The statement reads, “This practice is in stark contrast to drug policies for other sub-populations. For instance, all drugs must be evaluated for differences in people with renal and liver impairment, and significant incentives exist for testing to be undertaken in children once drugs have been proven safe and effective in adults.”
Drugs that may present issues for people with obesity include drugs in many familiar categories, including emergency birth control, depression, and pain relief. One example, Rexulti (brexpiprazole), is used to treat schizophrenia and depression. Used as labelled, Rexulti has been shown to underdose people with obesity, which could lead patients or their doctors to discontinue use. A person with undertreated schizophrenia or depression can be at risk of harming themselves or others or committing suicide. Another example is Noxafil, an antifungal treatment.
A second consequence of obesity can be a significant increase in drug half-life. An increased half-life may lead to inadvertent drug-drug interactions. For example, posaconazole, an antifungal marketed under the brand name Noxafil, was not fully tested in people with obesity prior to approval. The half-life of posaconazole is significantly longer in patients with obesity than in patients at a normal BMI. Because posaconazole is a strong inhibitor of CYP3A4, a liver enzyme that metabolizes a high percentage of all drugs, people with obesity are at risk of prolonged drug-drug interactions for weeks after stopping posaconazole. For instance, numerous cancer drugs already carry warnings to wait 3-5 drug half-lives after stopping a drug like posaconazole before resuming normal dosing. But drug labelling does not advise doctors that this phenomenon occurs in patients with obesity.
The statement continues, “In addition, we call on drug companies that are currently marketing drugs that have issues with safety or effectiveness for people with obesity at standard doses to update their labelling immediately to provide correct usage instructions for people with obesity.”
“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,” added Dr Jamy Ard, President-Elect of TOS, the leading professional society focused on obesity science, treatment, and prevention. “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 joint statement of support coincides with a special issue of the American College of Clinical Pharmacology’s Journal of Clinical Pharmacology, which includes a collection of articles addressing the need to study people with obesity as part of the drug development process.
To access the statement, please click here