An insulin-like drug being studied as a treatment for lipodystrophy may have a key advantage over other hormonal compounds in development. Compared to growth hormone-boosting agents TH9507 and Serostim, Virginia-based Insmed Inc.'s Iplex may also be able to a reduce blood glucose levels, a common problem in people with lipodystrophy.
Growth hormone, naturally produced by the pituitary gland, plays a major role in physiologic processes, including growth and metabolism. For example, growth hormone suppresses the ability of fat cells (adipocytes) to take up and accumulate circulating lipids.
Many of the metabolic effects of growth hormone are mediated primarily by insulin-like growth factor-1 (IGF-1), a hormone that is normally secreted from the liver.
Given that growth hormone can aid in the breakdown of fat, growth hormone supplements have been studied for the treatment of lipodystrophy, also known as HIV-associated Adipose Redistribution Syndrome (HARS). In fact, study results involving Theratechnologies' TH9507 and EMD Serono's Serostim (recombinant human growth hormone) have been encouraging.
Serostim, a synthetic version of growth hormone, is used to supplement natural growth hormone levels in the body to achieve a desired effect, such as significant fat loss. TH9507 works by boosting the production of natural growth homrone in the body.
Iplex, containing synthetic IGF-1 and a binding protein called IGFBP-3, boosts IGF-1 levels in the body and helps accelerate and intensify the metabolic effects of natural growth hormone.
Iplex was approved in the United States in December 2005 for the treatment of children with growth failure due to severe primary IGF-I deficiency. The drug is also being studied as a treatment for other diseases, including myotonic muscular dystrophy, retinopathy of prematurity, and amyotrophic lateral sclerosis (Lou Gehrig's disease).
A potential advantage of Iplex as a treatment for HARS may be its ability to control glucose homeostasis – the complex process by which blood sugars are maintained in the body. According to Geoffrey Allan, MD, President and Chief Executive officer of Insmed, "TH9507 and growth hormone reportedly either do not alter glucose homeostasis or exacerbate it, respectively. When considering that up to 40% of this population has impaired glucose homeostasis, then this property of Iplex becomes even more valuable."
The ongoing Phase II clinical trial is designed to evaluate the safety and effectiveness of Iplex in two groups of HIV-patients. In the first group, study volunteers will receive daily injections of Iplex, depending on their body weight (0.5 milligrams per kilograms [mg/kg]). The second group will receive daily 1.0 mg/kg doses.
The primary goals of the study are to determine the safety and tolerability of Iplex and its effects on visceral fat (fat deep within the body) and insulin sensitivity (improved sensitivity generally means better glucose homeostasis).
With respect to the effectiveness of Iplex, the press release did not reveal any specific details. The company only notes that, after three months of the once-daily 0.5 mg/kg dose, "there was a significant reduction in trunk fat and a positive downward trend in waist circumference when compared to baseline. Lipid profiles also tended to improve."
The effects of Iplex on glucose homeostasis were the most readily discussed. The study showed that 12 weeks of Iplex treatment, at a dose of 0.5 mg/kg/day, significantly increased IGF-I levels and was associated with significant improvements in fasting glucose levels, the amount of insulin secreted during an oral glucose tolerance test, and overall insulin sensitivity. The press release also notes that normal glucose tolerance was restored in half of the six patients diagnosed with impaired glucose tolerance (IGT) at the start of the study.
"We are very encouraged by these preliminary results with low-dose Iplex. We believe a product that improves fat distribution while also improving insulin sensitivity would be a valuable therapy for this patient population, and the positive effects on insulin sensitivity observed in this study are consistent with what we observed in our previous studies with Iplex in patients with diabetes," says Dr. Allen.
The next phase of the study is underway to explore an Iplex dose of 1.0 mg/kg/day given for six months.
Source: Insmed Inc.
