Description
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Obesity and Overweight: Developing Drugs and Biological Products for Weight Reduction.” This guidance provides recommendations to industry regarding the development of drugs and biological products regulated within the Center for Drug Evaluation and Research intended for reduction and long-term maintenance of body weight in patients with obesity or overweight. This guidance revises and replaces the draft guidance for industry “Developing Products for Weight Management” issued in February 2007.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
3Requires analytical comparability per ICH Q5E
FCDP consisting of two or more active ingredients combined at a fixed dosage
Investigational products intended for long-term weight maintenance; Efficacy of a weight-reduction drug in adults should be assessed by analyses of mean percentage change from baseline body weight
Stakeholders
2Assist sponsors in the nonclinical evaluation
Entity responsible for submitting applications under section 524B
Regulatory Context
Regulatory Activities
3Clinical assessment of weight-reduction drugs; Pivotal trials to examine efficacy and safety of weight-reduction drugs
Safety data commonly integrated across studies
Timeline for submitting pediatric study plans
Document Types
5Used to support labeling claims
Secondary efficacy endpoints intended for drug labeling
include the overall strategy for handling different intercurrent events... in the statistical analysis plan
Plan to account for higher prevalence of obesity in certain racial groups
Assessments of clinical outcomes from fit-for-purpose COA measures
Attributes
5expressed as kilograms of weight divided by height in meters squared (kg/m²); percentage change in body weight equals percentage change in BMI
Controlled across all clinically relevant secondary efficacy endpoints
Eligibility criteria for weight reduction trials
Body Mass Index used for weight classification and estimating adiposity
prespecified endpoints controlled for type 1 error
Technical Details
Substances
4Cardiovascular safety in overweight or obese patients
Effect on major adverse cardiovascular events
Cardiovascular outcomes in obesity without diabetes
Long-term effects on diabetes development
Testing Methods
10Columbia Suicide Severity Rating Scale
Graphs to illustrate the effect of the drug
Graphs to illustrate the effect of the drug
Recommended to facilitate assessment of integrated trial results
Analysis of percentage weight change from baseline
Analysis of percentage weight change from baseline
Help evaluate how sensitive observed results are to assumptions
DXA for measurement of body composition in pediatric subjects
measurement of body composition by DXA
Statistical considerations in clinical trials
Processes
3defined as a long-term reduction in excess adiposity
Pharmacokinetic studies required for FCDPs
Required before initiating long-term clinical studies
Clinical Concepts
10chronic disease characterized by excess adiposity; Defined as BMI at or above 30 kg/m² in adults or 95th percentile in children; patients with obesity or overweight; Developing drugs and biological products for weight reduction
Safety findings including deaths and post-mortem examinations
Weight gain caused by psychotropic or anticonvulsant agents
body mass index (BMI) classified as overweight who also have weight-related comorbidities; Defined as BMI 25-29.9 kg/m² in adults or 85th percentile in children; patients with obesity or overweight; Developing drugs and biological products for weight reduction
major comorbidities associated with excess adiposity; Common weight-related comorbidity
comorbidity associated with obesity; Common weight-related comorbidity; Weight-related comorbidity
comorbidity associated with obesity; Common weight-related comorbidity; Weight-related comorbidity
comorbidity associated with obesity
manifestations of obesity beyond excess adiposity
manifestations of obesity beyond excess adiposity
Identified Hazards
Hazards
1Confounding that can occur when pooling trials with different randomization ratios
Standards & References
External Standards
2Assessment and management of hypoglycemia
Hypoglycemia safety should be monitored and reported consistent with published guidelines
Specifications
4Efficacy endpoints in Phase 3 trials
Primary efficacy endpoint for weight-reduction drug trials
Primary efficacy endpoint for weight-reduction drugs
difference in mean percentage weight reduction between the investigational drug and control-treated groups is at least 5%
ICH References (3)
Guidance for drug interaction studies; Cited for drug-drug interaction evaluations
Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials
The Extent of Population Exposure to Assess Clinical Safety: For Drugs Intended for Long-term Treatment of Non-Life-Threatening Conditions
Related CFR Sections (1)
- 21CFR300.50§ 300.50 Fixed-combination prescription drugs for humans.
The Food and Drug Administration's policy in administering the new-drug, antibiotic, and other regulatory provisions of the Federal Food, Drug, and Cosmetic Act regarding fixed combination dosage form prescription drugs for humans is as follows:Read full regulation →
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