Tesamorelin Growth Hormone-releasing Factor Reduces Visceral Fat in Diverse Patient Groups

Tesamorelin (TH9507, brand name Egrifta), a recombinant form of human growth hormone-releasing factor, decreased the amount of visceral abdominal fat over 1 year in a variety of sub-populations of HIV patients with lipodystrophy, according to research presented at the recent 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). A related study found that fat loss measured by CT scans was reflected in reduced waist size and improved patient-reported body image.

Abdominal fat accumulation, which occurs in some HIV positive people taking antiretroviral therapy (ART), is a concern both in terms of appearance and potential cardiovascular risk.

Human growth hormone reduces visceral adipose tissue (VAT), or fat deep within the abdomen, but can cause side effects including elevated blood glucose, swelling, bone pain, and carpal tunnel syndrome. Instead of administering growth hormone directly, tesamorelin stimulates the pituitary gland in the brain to secrete the hormone, which results in more steady levels and fewer side effects.

As described in the March 1, 2010 Journal of Acquired Immune Deficiency Syndromes, patients receiving tesamorelin experienced an average visceral fat reduction of about 10% at 6 months, compared with less than 1% for placebo recipients; by 12 months, the reduction in the tesamorelin arm reached 18%. These benefits were soon lost, however, when people stopped taking the drug.

Subgroup Analysis

Earlier studies included mostly white men, making it unclear how results might apply to other groups. In the present analysis, Monica Zoltowska from Theratechnologies, Inc. and colleagues looked at the efficacy and safety of tesamorelin among sub-populations based on sex, age, race/ethnicity, viral hepatitis coinfection, use of ART, and HIV viral load.

In 2 Phase 3 multicenter trials, a total of 816 HIV positive participants with excess abdominal fat (lipohypertrophy) were randomly assigned (2:1) to receive 2 mg daily tesamorelin by subcutaneous injection or placebo for 26 weeks, followed by a 26-week extension phase to assess long-term safety and duration of effects. Some patients received tesamorelin for the full 52 weeks, while others switched from tesamorelin to placebo.

Overall, patient characteristics were similar between tesamorelin and placebo recipients. Most (85%) were men, about three-quarters were white, about 20% had viral hepatitis, and the average age was about 48 years. Just over 75% had undetectable viral load.

Results

• At 26 weeks, subgroup results were consistent with the overall finding that tesamorelin reduced visceral abdominal fat significantly more than placebo.
• No statistically significant treatment-by-covariate interactions were observed.
• No important differences in adverse events or side effect profiles were seen in any subgroups throughout the 52 total weeks of treatment.

These findings led the researchers conclude that "Tesamorelin significantly reduces visceral adipose tissue in different sub-populations of HIV-infected patients with abdominal lipohypertrophy, including women, patients with hepatitis, patients with detectable viral loads, and non-Caucasians," and did so "without any clinically meaningful differences in long-term safety."

Patient-reported Outcomes

In the second study, Julian Falutz from Montreal General Hospital and colleagues investigated whether the decrease in visceral adipose tissue observed with tesamorelin correlates with anthropometric measures and patient-reported outcomes in the same 2 trials of tesamorelin versus placebo.

Results

• By week 26, decreases in VAT (about -13% vs -2%) and waist circumference were significantly greater in the tesamorelin group than in the placebo group.
• Visceral fat decreases were consistently larger in the tesamorelin arm for people whose ART regimen included a NNRTI + NRTIs, those taking protease inhibitors + NRTIs, and those taking only NRTIs.
• Treatment with tesamorelin was also associated with clinically significant improvement in patient-reported outcomes such as belly appearance distress, and patient- and physician-rated belly profile.
• The strongest correlation was seen for waist circumference, followed by patient-rated belly profile.

"Tesamorelin significantly decreases VAT in HIV positive patients with excess abdominal fat," the researchers concluded.

"Assessment of VAT using CT scan is a research technique," they noted, "but the degree to which VAT is reduced in response to tesamorelin is apparent to patients based on significant reductions in waist circumference and improvements in body image that are highly correlated with reductions in VAT."

Tesamorelin is currently under review by the U.S. Food and Drug Administration. An FDA advisory committee unanimously recommended approval in June, but the expected late July decision date came and went with no action. The agency has now indicated that it expects to make a ruling later this fall.

Investigator affiliations:

H-228: Theratechnologies Inc., Montreal, Canada; EMD Serono, Boston, MA.

H-227: Montreal General Hospital, Montreal, Canada; Theratechnologies Inc., Montreal, Canadal; EMD Serono, Boston, MA; Massachusetts General Hosptal, Boston, MA.

9/28/10

References

M Zoltowska, J Morin, S Glyman, and G Soulban. Efficacy and Long-Term Safety of Tesamorelin (TH9507), a Growth Hormone-Releasing Factor (GRF) Analogue, in Sub-Populations of HIV-Infected Patients with Excess Abdominal Fat. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. Abstract H-228.

Reduction in Visceral Adipose Tissue (VAT) with Tesamorelin Correlates with Changes in Anthropometric, and Patient-Reported Outcome (PRO) Parameters in HIV+ Patients with Excess Abdominal Fat. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. Abstract H-227.