Treatment for at least 26 weeks resulted in significant reduction in Hard Belly
Continued treatment through 52 weeks maintained the reduction in Hard Belly
Patients receiving tesamorelin for the full 52-week study period maintained reduction of Hard Belly from weeks 26-52.
Patients on tesamorelin for injection for the full 52-week study period maintained reduction of Hard Belly from weeks 26–52
*Also known as excess abdominal fat
†Change from week 26 to week 52 in Hard Belly by treatment group (tesamorelin for injection week 0-52 or tesamorelin for injection week 0-26 and placebo week 26-52).
The results of the post-hoc analysis were not part of the New Drug Application (NDA), therefore were not reviewed by the FDA to support approval of EGRIFTA®.
In a post-hoc responder analysis of data from two multicenter, randomized, placebo-controlled trials:
Hard Belly significantly decreased from baseline in responders1,2
Two multicenter, randomized, double blind, placebo-controlled phase 3 studies in 816 HIV-infected patients with Hard Belly (N=412 in study 1; N=404 in study 2). Each study consisted of a main phase (26 weeks) followed by an extension phase (26 weeks).
Patients were randomized for each phase of the study.
Patients were on a stable anti-retroviral treatment regimen for at least 8 weeks prior to randomization. The primary efficacy endpoint was percent change from baseline in excess abdominal fat vs placebo at week 26. Changes in visceral adipose tissue vs week 26 baseline were also calculated at week 52. Amounts of excess abdominal fat and any changes in this were assessed using computed tomography (CT) scans at the L4-L5 vertebral level.
In multicenter, randomized, double-blind, placebo-controlled phase 3 studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (2:1 ratio) to receive tesamorelin for injection or placebo during the 26-week treatment phase. In the subsequent 26-week extension phase, patients who started on tesamorelin for injection were randomly assigned to continue receiving tesamorelin for injection or to switch to placebo, and patients who started on placebo were switched to tesamorelin for injection. In consultation with the FDA a decrease of ≥8% in excess abdominal fat area was determined to be clinically significant and was used to define “responders,” as specified a priori in the data analysis plan. Post-hoc analyses were performed to assess differences between responders and non-responders.1
In this post-hoc analysis, responders were determined independently at 26 and 52 weeks. A per-protocol analysis of adherent patients (>80% compliance with daily tesamorelin injections) was used to analyze clinical effects of tesamorelin. The per-protocol population included patients who had no major protocol violations and underwent ≥1 post-dose abdominal CT scan for excess abdominal fat measurement. Responders were individuals whose CT scans showed ≥8% reduction in excess abdominal fat from baseline.1
A post-hoc analysis of pooled data from two pivotal clinical trials of tesamorelin in HIV-infected patients with excess abdominal fat was not part of NDA to support approval of EGRIFTA®. Although the results differentiate responders from non-responders, they were not reviewed and approved by the FDA. Caution should be exercised in interpreting the results of the analysis.
References: 1. Stanley TL, Falutz J, Marsolais C, et al. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis. 2012;54(11):1642-1651. 2. Data on file. Theratechnologies, Inc. 3. Katzmarzyk PT, Mire E, Bouchard C. Abdominal obesity and mortality: The Pennington Center longitudinal study. Nutr Diabetes. 2012;2(e42):1-3. 4. Lemieux S, Prud’homme D, Bouchard C, et al. A single threshold value of waist girth identifies normal-weight and over weight subjects with excess visceral adipose tissue. Am J Clin Nutr. 1996;64:685-693.