CROI: Growth hormone stimulant TH9507 safe and effective in HIV lipodystrophy

A drug that stimulates the release of growth hormone reduced visceral fat in HIV-positive people by 20% over six months, without the glucose elevations or adverse events seen with recombinant human growth hormone, a large study has shown.

Stephen Grinspoon of Harvard Medical School presented final results of a study assessing the effect of growth hormone analogue TH9507 on visceral adipose tissue (VAT) in people with HIV on Monday at the Fourteenth Conference on Retroviruses and Opportunistic Infections in Los Angeles.

TH9507 is a peptide that helps stimulate the body’s production of growth hormone (GH) in a physiological manner rather than directly supplementing growth hormone. Preliminary studies show that it may have beneficial effects on the visceral fat accumulation seen with antiretroviral therapy (ART).

Visceral fat accumulation often occurs after HIV treatment is commenced, although studies comparing HIV-positive and HIV-negative men matched for age have failed to prove that it is a distinct feature of the HIV lipodystrophy syndrome.

However visceral fat accumulation contributes to the development of metabolic syndrome, and Stephen Grinspoon told a press conference that reducing abdominal fat is a justifiable clinical intervention because it has the potential to reduce cardiovascular risk.

The phase III study enrolled HIV positive people with abdominal fat accumulation related to ART. Participants were on a stable ART regimen and had documented abdominal fat accumulation: for men, a waist circumference (WC) of at least 95 cm and a waist-to-hip ratio (WHR) of at least 0.94; for women, a WC of at least 94 cm and a WHR of at least 0.88. Of the 412 participants, 275 were randomised to receive TH9507 2mg injected subcutaneously each day, while 137 received placebo injection.

Over the course of the 26-week study, change in VAT was measured by abdominal computed tomography (CT) scan. Other efficacy outcomes included triglyceride level, cholesterol-to-HDL ratio and IGF-I levels. Safety outcomes included glucose and insulin levels. The study was designed to have a 90% power to detect an 8% decrease in VAT between TH9507 and placebo.

At baseline, the population comprised 86% men, and the mean age of participants was 48 years. The mean WHR was 1.1 ± 0.1 and the mean WC was 104 ± 10 cm. Of all participants, 19% had type II diabetes or glucose intolerance.

At week 26, 80% of participants remained in the study. Analysis revealed a significant decrease in VAT among the group receiving TH9507, -27.8cm², compared with the placebo group, +4.9cm² (p

Lipid profiles improved in the group receiving TH9507, with significant decreases in triglyceride level and cholesterol-to-HDL ratio. Triglyceride levels fell -0.6 ± 1.7 mmol/l with TH9507 while increasing +0.1 ± 1.3 mmol/l with placebo (p

Mean IGF-I increased significantly with TH9507 (+80% vs -5% with placebo, p

The authors conclude that TH9507 decreased VAT and improved lipid profile and “may represent a novel treatment strategy for HIV patients with central fat accumulation, including those with impaired glucose homeostasis.”

Discussing the findings, Stephen Grinspoon noted that TH9507 is less likely to interfere with glucose levels because it regulates the secretion of human growth hormone from the pituitary rather than flooding the body with supplementary growth hormone (which disrupts the feedback mechanism that regulates glucose levels, amongst other things).

H e also noted that the lipid-lowering effect seen in the TH9507 arm was better than that seen in many patients treated with lipid-lowering drugs, even though TH9507 is not a lipid-lowering agent.

A second phase III study is now taking place in Europe, and if the results confirm the findings of the first study, manufacturer Theratechnologies will seek a license for the use of TH9507 in treatment of HIV-associated visceral fat accumulation.