Phase II results show ThGRF could be safe, effective treatment for lipodystrophy, says company

Theratechnoligies, a Canadian biotech company, is trumpeting the preliminary Phase II trial results of its ThGRF, a stabilised analogue growth hormone-releasing factor (GRF) that looks promising for the treatment of HIV-associated lipodystrophy patients with excessive visceral fat.

The preliminary results suggest that ThGRF is safe and effective, concentrating its effect on reducing visceral fat while preserving subcutaneous fat. This would make it particularly useful in treating people with an accumulation of visceral fat (lipohypertrophy) together with a loss of subcutaneous fat (lipoatrophy). It demonstrated good glycaemic control, even among glucose intolerant and diabetic patients. About 40% of HIV-associated lipodystrophy patients are either glucose intolerant or diabetic.

ThGRF induces the production and secretion of growth hormone in a specific, physiological and pulsatile fashion, which, says the company, makes it a strong candidate as a potential treatment for many diseases related to aging and obesity as well as HIV-associated lipodystrophy.

The double-blind, randomised, placebo-controlled study conducted in seven centres in Canada and the USA, enrolled 61 patients, all on stable antiretroviral therapy, in parallel groups, who received a daily subcutaneous injection of ThGRF 1 mg, 2 mg or placebo, over a period of 12 weeks.

The researchers report that the 2 mg dose produces a marked increase in levels of IGF-1 (a dependable indicator of bioavailable growth hormone in the human body) (+80%, P < 0.01 vs placebo), and “highly significant” effects on body composition (lean body mass: +1.7kg, P < 0.01 vs placebo; total body fat mass: 1.4 kg, P < 0.02 vs placebo).

Dr Steven Grinspoon, Director of the Programme in Nutritional Metabolism, and Associate Professor of Medicine at Harvard Medical School and Lead Investigator for the US, said: “The selectivity on visceral fat mass as well as the decrease in the VAT/SAT [visceral fat/subcutaneous fat] ratio are noteworthy … and suggest that the physiological mode of action of ThGRF translates into clinical advantages over other approaches for patients with HIV-associated lipodystrophy. ThGRF may also prove useful to alter fat distribution from the trunk and viscera in non-HIV-infected patients with the metabolic syndrome.”

A company statement says: “Based on these positive results, the company and its clinical experts consider that ThGRF is well suited for Phase III testing as a novel approach to treat HIV lipodystrophic patients with excessive visceral fat, an unmet clinical need.”

Comment

The same results however with the potential of reducing subcutaneous fat have been reported for recombinant human Growth Hormone (r-hGH).

It would be interesting to know the effect of ThGRF on glucose metabolism or the frequency of arthralgia, two adverse events of r-hGH. In addition a reduction 1.4 kg visceral fat is fairly moderate and is in the range of the changes reported for exercise or metformin, and less than that reported for r-hGH.