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  EACS - 12th European AIDS Conference
November 11-14, 2009
Cologne, Germany
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Metabolic Effects of Tesamorelin (TH9507), a Growth Hormone-Releasing Factor Analogue, in HIV-infected Patients with Excess Abdominal Fat over a Period of 52 Weeks. A Pooled Analysis of 2 Multicenter, Double- blind, Placebo-controlled Phase 3 Trials with 816 Randomized Patients
  Reported by Jules Levin
EACS Oct 31-Nov 3 2009, Cologne Germany
Julian Falutz1, Jean-Claude Mamputu2, Diane Potvin2, Graziella Soulban2, Sophie-Elise Michaud2, Christian Marsolais2, Hani Assaad2, and Steven Grinspoon3
1Montreal General Hospital, McGill University Health Centre, Montreal, Canada; 2Theratechnologies Inc., Montreal, Canada;
3Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Administration of 2 mg tesamorelin to HIV-infected patients with excess abdominal fat for 52 weeks resulted in improved body composition, including maintenance of VAT loss and preservation of subcutaneous adipose tissue and limb fat. Treatment with tesamorelin was also associated with a clinically significant decrease in triglycerides and improvement in patient reported outcomes. In addition, tesamorelin was well tolerated, without significant clinical effect on glucose parameters. Overall, these results suggest that tesamorelin may be beneficial for the treatment of HIV patients with excess abdominal fat.


HIV patients treated with antiretroviral therapy (ART) often experience increased visceral adipose tissue (VAT). We report pooled analysis from 2 randomized, placebo-controlled Phase 3 studies of tesamorelin in ART-treated HIV patients with excess abdominal fat.
Method: Patients were randomized to receive tesamorelin 2 mg (N=543) or placebo (N=263) subcutaneously daily. At Week 26, patients initially on tesamorelin were re-randomized to 2 mg tesamorelin (T-T group, N=246) or placebo (T-P, n=135) for an additional 26 weeks, whereas patients on placebo were switched to tesamorelin (P-T, N=197). The primary endpoint was the percent change in VAT by CT-scan at Week 26. Secondary endpoints included lipids, IGF-1 and safety. At Week 52, endpoints were safety and duration of effects on VAT.
Results: Baseline age was 48±7 (mean±SD) years and waist circumference 105±9cm.
At Week 26, VAT decreased significantly in tesamorelin-treated patients (-13.1±21.1% P<0.001 vs. placebo), while no clinically significant changes were observed in limb fat by DEXA (0.2±13.2%, P=0.001 vs. placebo).
No significant changes were observed in abdominal SAT (0.7±15.5%, P=0.08 vs. placebo). Treatment with tesamorelin was associated with a significant decrease in triglycerides (-0.4±1.6 mmol/L, P<0.001 vs. placebo).
Mean IGF-1 levels increased within physiological range in tesamorelin-treated patients (84.1±101.3%, P<0.001 vs. placebo).
At Week 52, improvements in VAT and triglycerides observed at Week 26 were sustained in the T-T group (-17.5±23.3% and -0.5±2.0 mmol/L, respectively, P<0.001 vs. baseline), while SAT was preserved.
Patients in the T-P group regained VAT (0.3±26.3%, P=0.18 vs. baseline). Treatment with tesamorelin was overall well tolerated.
No clinically significant differences were observed between groups in glucose parameters at both Weeks 26 and 52.
Conclusion: Treatment with 2 mg tesamorelin daily for up to 52 weeks results in sustained VAT reduction, preservation of SAT, improvement in triglycerides and is overall well tolerated without significant changes in glucose parameters.
HIV-infected patients treated with antiretroviral therapy (ART) often demonstrate HIV lipodystrophy, which is characterized by body changes, such as fat accumulation in the abdomen and metabolic abnormalities including dyslipidemia and/or insulin resistance, which may increase cardiovascular risk (1-3). Results from two Phase 3 studies in HIV-infected patients with excess abdominal fat demonstrated that treatment with tesamorelin (TH9507), a stabilized analogue of growth hormone-releasing factor (GRF) or growth hormone-releasing hormone (GHRH), for 52 weeks led to a significant reduction in VAT, improvement in triglycerides as well as patient reported outcome (PRO) related to body image (4,5). Here we report the main efficacy end safety endpoints over a period of 52 weeks for the combined Phase 3 studies.



The re-randomization ratio T:P was 3:1 in LIPO/010 Extension and 1:1 in CTR-1012 ENDPOINTS
Week 26: Primary endpoint: 8%
percent change in VAT from baseline by computed tomography (CT) scan at L4-L5
Secondary endpoints:Triglycerides, total cholesterol/HDL cholesterol ratio, IGF-1 levels, patient outcomes related to belly image, safety (glucose, insulin, adverse events and others)
Week 52: Primary endpoint: Safety (glucose, insulin, adverse events and others) Other endpoints: Duration of effect on VAT following a 26-week treatment with 2 mg tesamorelin; 52-week efficacy data on VAT
The efficacy endpoints were analyzed on the basis of data for patients who had received at least one dose of study drug with the last observation carried forward for those patients not completing the study, to determine treatment differences between tesamorelin and placebo at Week 26. Within-treatment comparisons were performed in each treatment group using a repeated-measures analysis of variance. Between-treatment comparisons were performed for T-T vs. T-P using an ANCOVA. Evaluation of safety at Week 52 of treatment was based on the safety population, which included all randomized patients who received at least one dose of a study drug during the extension phase of the study.



a, W: White; AA: African American/Black; H: Hispanic




Table 2. Body composition parameters over 52 weeks. Data are mean ± SD. *P<0.001 vs. Baseline. P< 0.001 vs. Week 26.


Figure 3. Change from baseline in patient reported outcome parameters at Week 52. Data are mean ± SEM. *P<0.01 vs. Baseline. Displayed P-values are for the between group comparisons ( T-T vs. T-P).


Table 3. Changes from baseline in metabolic parameters after 26 and 52 weeks of treatment. Data are mean ± SD.