- Developing Products for Weight Management
- March 7, 2007 | Author: Joseph P. McMenamin
- Law Firm: McGuireWoods LLP - Richmond Office
In February, 2007, CDER published a draft Guidance for Industry: “Developing Products for Weight Management.” The Guidance revised an earlier one for the clinical evaluation of weight control drugs issued September 19, 1996. The purpose of the new draft is to incorporate scientific and clinical advances made since 1996 in the development of weight management drugs. The document seeks to provide advice on conducting studies to evaluate the efficacy and safety of products for weight management in patients with medication-induced weight gain and in obese children as well.
Because excess adiposity may influence a product’s metabolism and disposition, CDER recommends that the pharmacokinetics profile of a weight-management product be examined in patients with a broad range of body-mass indices (“BMIs”). It also suggests that early phase clinical studies include a range of doses and be designed to identify no-effect and maximally tolerated doses. CDER calls for phase 2 trials to last long enough to capture the maximal or near-maximal weight loss effects of the active doses.
The Guidance issues recommendations on minimal BMIs for patients in both efficacy and safety studies and in later clinical trials; what efficacy endpoints should be used; numbers of subjects needed to demonstrate safety, as opposed to efficacy; and how to rule out loss of lean body mass as opposed to fat content. The Guidance also touches on clinical assessments in pediatric patients and what statistical methods are preferred.
Since many overweight patients are also being treated for hypertension, diabetes and so forth, and since weight loss may improve these co-morbidities, the Center says that the proportion of subjects who experience a meaningful dose-reduction or complete withdrawal of their concomitant medications should also be considered.
In the Center’s view, fixed-dosed combination products should demonstrate efficacy superior to those of the components used alone.
In assessments of children, CDER calls for performing pharmacokinetic studies before clinical ones; using patients with age- and sex-matched BMI’s at the 95th percentile or greater; starting with adolescents before younger children; starting with patients with one or more weight-related comorbidities before lower risk patients; correlating data with height; and validating assessments of neuropsychiatric function in studies of centrally acting weight-management products.
Perhaps the most important statement is the Guidance is a bright-line test of efficacy. The Guidance says that if after one year of treatment either one of two outcomes occurs, the product is effective: 1) The difference in mean weight loss between the active-product and placebo-treated groups is at least 5 percent and the difference is statistically significant; or 2) The proportion of subjects who lose 5 percent of baseline body weight or more in the active-product group is at least 35 percent and approximately double the proportion in the placebo-treated group, and the difference between groups is statistically significant.
Commenters have 60 days to respond to this draft Guidance. Companies making products to control weight, especially among patients with medication-induced weight gain or for children, may want to take the opportunity to do so.