The Food and Drug Administration (FDA) has issued draft guidance outlining recommendations for the development of drugs and biological products aimed at weight reduction and long-term weight maintenance in individuals with obesity or overweight. A key proposal is that investigational antiobesity medications should demonstrate a minimum of 5% weight loss, sustained for one year at the maintenance dose, to be considered effective.
The draft guidance, titled "Obesity and Overweight: Developing Drugs and Biological Products for Weight Reduction," provides a structured framework for the pharmaceutical industry to develop safe and effective weight management therapies. It emphasizes the importance of achieving long-term weight reduction to improve overall health outcomes. The FDA encourages assessment of the effect of drugs on the manifestations of obesity or overweight beyond excess adiposity (eg, obstructive sleep apnea, osteoarthritis), this guidance focuses on study designs and endpoints to assess the effectiveness of drugs on sustained weight reduction itself in patients with obesity or overweight.
Clinical Trial Design and Endpoints
The guidance details key aspects of clinical trial design, including the selection of appropriate adult and pediatric participants, principles for Phase 1 and Phase 2 trials, and comprehensive considerations for Phase 3 trials. These considerations encompass trial design, sample size, duration, efficacy endpoints, safety evaluations, and statistical principles.
The benchmark for efficacy will be a statistically significant difference between the investigational drug- and control- treated groups of 5% maintained after 1 year of treatment.
Special Populations and Combination Therapies
The draft guidance specifically addresses trial considerations for evaluating antiobesity medications in individuals with type 2 diabetes (T2D), acknowledging the potential for reduced efficacy and increased risk of hypoglycemia in this population. It recommends that manufacturers evaluate sufficient numbers of individuals with comorbid obesity and T2D, either in dedicated trials or within adequately powered subgroups of larger weight reduction trials.
Additionally, the guidance highlights the assessment of antiobesity medications when used in combination, when explored for reduction of medication-induced weight gain, and trial considerations for assessment of pediatric patients.
Safety Considerations
Recognizing the importance of safety, the FDA emphasizes the need for comprehensive evaluations of cardiovascular effects, fit-for-purpose neuropsychiatric assessments, and investigations into the immunogenic potential of therapeutic proteins. The draft guidance also addresses the growing concern of abuse liability associated with centrally acting weight-reduction drugs, encouraging sponsors to conduct nonclinical and clinical studies to assess this risk and engage in discussions with the FDA during early drug development phases.
Public Comment and Next Steps
The draft guidance is currently open for public comment, allowing stakeholders from various sectors to provide input and refine the recommendations. The FDA encourages electronic or written submissions within 90 days of the document's publication. While the guidance does not establish legally enforceable responsibilities, it represents the agency's current thinking on the topic and serves as a set of recommendations for manufacturers developing weight reduction products.
