Efficacy
The results for the 16 week active weight loss period of treatment with enobosarm 3 mg or placebo in combination with semaglutide:
| • | The enobosarm 3 mg + semaglutide group met the primary endpoint of study, preservation of total lean mass, with a statistically significant 100% average preservation of total lean mass compared to placebo + semaglutide at 16 weeks. |
| • | Enobosarm + semaglutide treatment resulted in dose dependent greater loss of fat mass compared to placebo + semaglutide with the enobosarm 3 mg group having a 12% greater fat loss at 16 weeks. |
| • | Even with having preserved lean mass, enobosarm 3 mg + semaglutide treatment resulted in a similar mean body weight loss as semaglutide alone at 16 weeks. However, it should be noted, in a subset analysis of the subjects receiving enobosarm 3 mg and had a baseline BMI ≥ 35, incremental weight loss was observed at 16 weeks: |
| • | There was weight loss of -4.7% for semaglutide versus -5.58% for enobosarm 3 mg + semaglutide treatment group. |
| • | Proportion of patients that lost at least 5% of body weight at 16 weeks was 47.4% for semaglutide vs 65.4% for enobosarm 3 mg + semaglutide treatment group. |
| • | This weight loss occurred even with 84% preservation of lean mass in this subset of patients receiving semaglutide on enobosarm 3 mg. |
| • | The tissue composition of the total body weight lost on average was 34% lean mass and 66% fat mass in the placebo and semaglutide group, whereas for the enobosarm 3 mg + semaglutide group, the weight loss was 0% lean mass and 100% fat mass. |
| • | Physical function was measured by the Stair Climb Test. A prespecified responder analysis was conducted using a greater than 10% decline in stair climb power as the cut off at 16 weeks which is a decline that represents an approximate 7 to 8 years of loss of stair climb power function that naturally occurs with aging, but it occurred in 16 weeks. |
| • | Semaglutide alone resulted in a loss of physical function as 44.8% of the placebo + semaglutide group had at least a 10% decline in stair climb power physical function at 16 weeks. The Phase 2b QUALITY study is the first to confirm that older patients with obesity receiving a GLP-1 RA had a significant and relevant physical function decline as early as 16 weeks on treatment. |
| • | In contrast, enobosarm 3 mg treatment reduced the proportion of patients receiving semaglutide to 17.6% who experienced ≥10% decline in stair climb power. This represents a 59.8% relative reduction in proportion of patients receiving enobosarm who experienced ≥10% decline in stair climb power. |
Results forthe Maintenance Extension portion of the study, where all patients discontinued semaglutide treatment, but continued receiving placebo, enobosarm 3 mg as monotherapy for 12 weeks:***** *
| • | The placebo monotherapy group regained 43% of body weight that was previously lost during the Phase 2b QUALITY study for a mean percent change of 2.57% (5.06 lbs) in body weight, compared to 1.41% (2.73 lbs) for the 3 mg enobosarm group. This means that the 3 mg enobosarm monotherapy significantly reduced the body weight regained by 46% after discontinuation of semaglutide. |
| • | By the way, the mean tissue composition of body weight regained was 100% lean mass, not fat for the enobosarm 3 mg compared to 28% fat and 72% lean mass in the placebo group. |
| • | In fact, by end of the 28 week study, enobosarm 3 mg plus semaglutide followed by enobosarm 3 mg monotherapy regimen was more effective in preserving 100% lean mass and in losing 58% more fat compared to placebo plus semaglutide followed by placebo monotherapy. |
