Industry supports FDA’s draft guidance on weight management drugs, suggests some refinements

The pharmaceutical industry generally supports draft guidance from the US Food and Drug Administration (FDA) on the development of drugs and biologics for weight reduction but would like to see greater flexibility regarding patient enrollment and the size of safety studies.

The proposed guidance on developing drugs and biological products for weight reduction was issued in January 2025 (RELATED: FDA proposes update to 18-year guidance on developing weight loss drugs, Regulatory Focus 7 January 2025).

The draft guidance aims to update a 2007 document on developing products for weight management. Recently, FDA-approved drugs with chronic weight management indications such as Wegovy (semaglutide) and Zepbound (tirzepatide) have gained significant popularity and commercial success. The FDA has revised this guidance to reflect the new knowledge and insights gained regarding these drugs since the original document was published.

FDA received 27 comments in response to the draft guidance. The deadline for commenting was 8 April.

Many commenters approved the FDA's decision to recognize obesity as a chronic disease. A former draft guidance issued in 2007 defined obesity as a “chronic, relapsing health risk defined by excess body fat. The pathogenesis of obesity involves the interaction of genetic, environmental, and behavioral factors.”

The recent guidance defines obesity as “a chronic disease characterized by excess adiposity. Excess adiposity is associated with an increased risk of death and major comorbidities such as type 2 diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, nonalcoholic steatohepatitis, gallbladder disease, osteoarthritis of the knee, sleep apnea, and some cancers.”

Eli Lilly, maker of Zepbound, said the guidance “clearly” characterizes obesity as a chronic disease. They emphasized that “with the broadening impact of the obesity epidemic on public health and a renewed focus on development of novel therapies to treat obesity, FDA’s clear acknowledgment of obesity as a disease is in the best interest of patients and will help facilitate development of products and practices to address this growing public health crisis.”

NovoNordisk, maker of Wegovy, said FDA's recognition of obesity as a chronic disease “rightfully aligns with current scientific understanding. And, importantly, recognizing obesity as a chronic disease can help reduce stigma and encourage patients to seek treatment options.” However, the company urged FDA to change the title of the guidance from “weight reduction” to “treatment of obesity” to better reflect that these drugs “are intended to treat the disease of obesity and its multiple comorbidities.”

Eliminate fixed enrollment number

The Pharmaceutical Research and Manufacturers of America (PhRMA) and Eli Lilly both urged the FDA to remove the requirement that clinical trials for obesity drugs must enroll 1,500 participants in a placebo group to assess the safety of an obesity drug. They argue that this number should be flexible, allowing for smaller participant groups.

“Lilly believes that this is rapidly becoming impractical and is a key area where FDA should consider updating the regulatory requirements. Rather than being prescriptive by suggesting a ‘one-size-fits-all approach,’ Lilly recommends FDA adopt a more flexible risk-based approach to determining the appropriate number of patients assigned to placebo to assess safety or recommend that sponsors use alternative statistical approaches that take prior scientific knowledge into consideration,” according to the company’s submitted comment. “Indeed, current studies of new obesity medications are experiencing challenges in enrollment and retention in placebo arms due to the effectiveness of these drugs.”

PhRMA also recommends that the FDA adopt a more flexible approach to patient enrollment. “As more effective treatments are developed, large placebo groups may not be warranted, and thus smaller placebo groups would be consistent with ethical principles promoting the minimization of patients receiving placebo when proven treatments exist.”

Eliminate fixed number for safety assessments

Industry members also recommended that the FDA adopt a more flexible method for determining the number of patients to monitor in follow-up safety assessments.

The FDA recommends that 3,000 subjects be studied for at least one year after treatment to assess the safety of a weight reduction drug.

PhRMA said that it supports “a more flexible and risk-based approach, as opposed to a specific and rigid threshold, that enables both leveraging sponsors’ own prior data and more patient-centric clinical trials (e.g., trials allowing more flexibility in dosing that reflects real-world usage). This could also, for example, allow for data generated during up/down titration period to support a safety assessment.”

NovoNordisk also “strongly encourages FDA to allow a more flexible approach to the size of the safety database (for both patients on placebo and on the investigational drug) depending on the individual development program and existing data that could be leveraged as appropriate.”

Limitations of BMI supported

The industry supports the FDA's recognition of the limitations of body mass index (BMI) in measuring obesity. FDA said in the guidance that BMI has “several limitations.”

FDA said that “although higher BMI is strongly associated with increased body fat, BMI is not a direct measure of body fat, and it does not inform the distribution of excess body fat. In clinical practice, supplementing BMI with other anthropometric measures, such as waist circumference, may be appropriate in certain individuals.”

PhRMA states that “we appreciate FDA’s recognition in the draft guidance of the limitations associated with body mass index (BMI) as a measure of obesity. These limitations have also been highlighted in recent scientific publications.”

Lilly also expressed support for FDA's recognition of certain limitations associated with BMI. Yet Lilly said there were other limitations not listed, such as the inadequacy of BMI across all racial and ethnic groups and variations in BMI based on age and biological sex.

Lilly wrote that “many medical societies as well as the leading experts in the field agree that the use of BMI plus an anthropometric measure of central adiposity is more appropriate than using BMI alone. Current BMI-based measures of obesity can both underestimate and overestimate adiposity and provide inadequate information about health at the individual level.”

Comments

Industry supports FDA’s draft guidance on weight management drugs, suggests some refinements

Related topics

Recommended content

Welcome to the new RAPS Digital Experience