Tesamorelin Reduces Visceral Fat by up to 18% in HIV-Infected Men

Becky McCall

November 19, 2009

November 19, 2009 (Cologne, Germany) — Visceral fat in HIV-infected men is reduced 18% and effects are sustained over 52 weeks by the growth hormone precursor tesamorelin, researchers announced here at the 12th European AIDS Conference/European AIDS Clinical Society (EACS).

Steven Grinspoon, MD, professor of medicine at Harvard University Medical School and director of the Neuroendocrine Clinical Centre at Massachusetts General Hospital in Boston, led an analysis of 2 multicenter double-blind placebo-controlled phase 3 trials and presented the results here at the Best Posters session.

One of the negative consequences of living longer with HIV is that up to 25% of patients experience undesirable changes in body fat composition, including a loss of fat in the extremities and a gain in the amount of deep visceral fat. In HIV, there are emerging data showing that this fat is linked to coronary artery disease.

Strategies to reduce this fat include lifestyle changes (diet and exercise); however, these are not 100% effective and are often difficult to follow, Dr. Grinspoon observed.

"We find that people with visceral fat have relatively low-growth hormone levels, and these further contribute to accumulation of visceral fat in a vicious cycle. We consider the best way to break the cycle is to give a drug to stimulate natural production of growth hormone." The drug under study was tesamorelin, a precursor to growth hormone.

The study presented at EACS is the culmination of 6 years of work combining 2 pivotal phase 3 randomized placebo-controlled studies into 1 analysis of pooled data. The first study was published in The New England Journal of Medicine in 2007 (N Engl J Med. 2007;357:2359-2370); the second paper in the series is currently in press.

In a 2:1 distribution, 543 patients were randomized to receive tesamorelin 2 mg daily, and 263 to receive placebo. Average age at baseline was 48 years, and average waist circumference was 105 cm.

Change in percentage of visceral fat at 26 weeks was the primary end point. After 26 weeks, participants in the placebo group were transferred to the tesamorelin group and those in the tesamorelin group were rerandomized so that half remained in the tesamorelin group and half were transferred to the placebo group.

"This study design allowed us to see what happens if people stay on the drug for 52 weeks, and also to observe changes in those who were on the drug for the first period of study and then came off for the second half."

At 26 weeks, tesamorelin was found to reduce visceral fat by 13% (–13.1 ± 21.1%; P < .001), compared with placebo.

"We found that if people stay on the drug, then visceral fat drops further; this was very significant, dropping by almost 18% in 52 weeks. It also showed that once off the drug, the change is reversed," Dr. Grinspoon announced.

"This is a large clinical effect that was accompanied by other positive effects, such as significantly reduced triglycerides over 26 weeks [–0.4 ± 1.6 mmol/L; P < .001 vs placebo], and resulted in [insulin-like growth factor] levels increasing to within physiological range in treated patients," said Dr. Grinspoon.

There were no significant safety events or changes to glucose parameters reported. "Tesamorelin is not approved by the [US Food and Drug Administration] yet, but it is an exciting new strategy for controlling visceral fat accumulation. The results come from a rigorously done placebo-controlled study in a large number of patients of a novel therapy," concluded Dr. Grinspoon.

Esteban Martinez, MD, an infectious disease specialist from the University of Barcelona, in Spain, chaired the session. He explained that control of abdominal fat in the HIV-infected population is an unmet need.

"Currently available interventions have included diet and exercise, switching [antiretroviral therapy], metformin (potentially useful, but decreases subcutaneous fat and contributes to worse lipoatrophy), and growth hormone, which is also potentially useful, but not [approved] for this indication and has an increased risk of diabetes. None of them has been satisfactory enough to be widely recommended in clinical practice."

"Overall, tesamorelin was well tolerated, with local immune-mediated mild reactions at the injection site in less than 5% of the patients as the only remarkable side effect. The effects on visceral adipose tissue were seen as long as the patients were receiving the drug, and they disappeared upon tesamorelin discontinuation, suggesting that some kind of intermittent schedule should be explored to be clinically applied," Dr. Martinez told Medscape HIV/AIDS.

Dr. Grinspoon reports receiving research funding and consulting fees from Theratechnologies in the past, but not currently. Dr. Martinez reports receiving research funding, consulting fees, or lecture sponsorships from or serving on advisory boards for Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck Sharp & Dohme, Theratechnlogies, and Tibotec.

12th European AIDS Conference/European AIDS Clinical Society (EACS): Abstract 9.3. Presented November 13, 2009.

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