Egrifta (tesamorelin for injection)

Egrifta contains tesamorelin, an analog of human growth hormone-releasing factor (GRF). Tesamorelin binds and stimulates human GRF receptors with similar potency as the endogenous GRF. Growth hormone-releasing factor is a hypothalamic peptide that acts on the pituitary somatotroph cells to stimulate the synthesis and pulsatile release of endogenous growth hormone, which is both anabolic and lipolytic.

Egrifta is specifically indicated for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy.

Egrifta is supplied as a sterile, white to off-white lyophilized powder for reconstitution designed for subcutaneous administration. The recommended initial dose is 2 mg injected subcutaneously once a day. The recommended injection site is the abdomen. Injection sites should be rotated to different areas of the abdomen. Egrifta should not be injected into scar tissue, bruises or the navel.

FDA Approval
The FDA approval of Egrifta was based on two multicenter, randomized, double-blind, placebo-controlled studies in HIV-infected patients with lipodystrophy and excess abdominal fat (abdominal lipohypertrophy). Both studies consisted of a 26-week Main Phase and a 26-week Extension Phase. The subjects were randomized to receive 2 mg Egrifta or placebo subcutaneously daily for 26 weeks. The primary efficacy assessment for each of these studies was the percent change from baseline to Week 26 (Main Phase) in visceral adipose tissue (cm2), as assessed by computed tomography (CT) scan at L4-L5 vertebral level. In both studies, Egrifta- treated patients completing the 26-week treatment period were re-randomized to blinded therapy with either daily placebo or 2 mg Egrifta for an additional 26-week treatment period (Extension Phase) in order to assess maintenance of VAT reduction and to gather long-term safety data.
Study One
Main Phase
This study randomized 412 subjects. At Week 26, treatment with Egrifta resulted in a reduction from baseline in mean trunk fat of 1.0 kg compared with an increase of 0.4 kg in the placebo group. In addition, Egrifta resulted in an increase from baseline in mean lean body mass of 1.3 kg compared with a decrease of 0.2 kg in the placebo group.
Extension Phase
This study re-randomized 207 subjects. Those treated with Egrifta showed no change between Weeks 26 and 52 in mean trunk fat (increase of 0.1 kg vs. increase of 1.4 kg in placebo group) nor was there a change from Week 26 baseline in mean lean body mass (decrease of 0.1 kg vs. decrease of 1.8 kg in placebo group).
Study Two
Main Phase
This study randomized 404 subjects. At Week 26, treatment with Egrifta resulted in a reduction from baseline in mean trunk fat of 0.8 kg compared with an increase of 0.2 kg in the placebo group. In addition, Egrifta resulted in an increase from baseline in mean lean body mass of 1.2 kg compared with a decrease of 0.03 kg in the placebo group.
Extension Phase
This study re-randomized 177 subjects. Those treated with Egrifta showed no change between Weeks 26 and 52 in mean trunk fat (decrease of 0.5 kg vs. an increase of 1.09 kg in placebo group) nor was there a change from Week 26 baseline in mean lean body mass (increase of 0.1 kg vs. decrease of 1.7 kg in placebo group).
In both studies, there was no adverse effect of Egrifta on lipids or subcutaneous adipose tissue and Efrifta did not adversely alter antiretroviral effectiveness, such as mean circulating levels of CD4 counts or HIV-1 RNA (viral load).

Adverse events associated with the use of Egrifta may include, but are not limited to, the following:

• Arthralgia
• Injection site erythema
• Injection site pruritis
• Pain in extremity
• Peripheral edema
• Myalgia

Egrifta contains tesamorelin, an analog of human growth hormone-releasing factor (GRF). Tesamorelin binds and stimulates human GRF receptors with similar potency as the endogenous GRF. Growth hormone-releasing factor is a hypothalamic peptide that acts on the pituitary somatotroph cells to stimulate the synthesis and pulsatile release of endogenous growth hormone, which is both anabolic and lipolytic. GH exerts its effects by interacting with specific receptors on a variety of target cells, including chondrocytes, osteoblasts, myocytes, hepatocytes, and adipocytes, resulting in a host of pharmacodynamic effects.

Falutz J, Mamputu JC, Potvin D, Moyle G, Soulban G, Loughrey H, Marsolais C, Turner R, Grinspoon S Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. The Journal of clinical endocrinology and metabolism 2010 Sep;95(9):4291-304

Ferdinandi ES, Brazeau P, High K, Procter B, Fennell S, Dubreuil P Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic & clinical pharmacology & toxicology 2007 Jan;100(1):49-58

For additional information regarding Egrifta or abdominal fat in HIV-infected patients with lipodystrophy, please visit the Egrifta web page.