Originally published by our sister publication Infectious Disease Special Edition

The FDA approved the supplemental Biologics License Application for the F8 formulation of tesamorelin for injection (Egrifta WR, Theratechnologies) to treat adults with HIV who have excess visceral fat. 

Tesamorelin for injection is a growth hormone–releasing factor analog that acts on pituitary cells in the brain to stimulate the production and release of endogenous growth hormone. Tesamorelin for injection is the only medication approved in the United States for the reduction of excess abdominal fat in adults with HIV who have lipodystrophy. 

The new formulation is a daily injectable but only needs weekly reconstitution. It requires less than half the administration volume as the current F4 formulation (Egrifta SV), which is reconstituted daily.

Pharmacokinetic studies have shown bioequivalence of the new formula to the old one. The most commonly reported adverse reactions of tesamorelin for injection include arthralgia, injection site reactions, pain in extremity, peripheral edema and myalgia.

Two multicenter, randomized, double-blind, placebo-controlled studies were conducted in people with HIV who were suffering from lipodystrophy and abdominal lipohypertrophy. Study 1 and Study 2 consisted of a 26-week main phase and 26-week extension phase, respectively. People 18 to 65 years of age with a waist circumference of 37.4 inches and waist-to-hip ratio of at least 0.94 for men as well as a 37.0-inch waist circumference and at least 0.88 waist-to-hip ratio for women, respectively, were included in the studies. The patients also had a fasting blood glucose (FBG) of less than 150 mg/dL. Patients were randomly assigned to a 2-mg dose of tesamorelin (1-mg/vial formulation) 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 in visceral adipose tissue (VAT), as assessed by CT of the L4-L5 vertebral level.

Secondary end points included changes from baseline in patient-reported outcomes related to body image, triglycerides, ratio of total cholesterol to high-density lipoprotein cholesterol, insulin-like growth factor 1 levels and safety parameters. Other end points included changes from baseline in waist circumference, abdominal subcutaneous tissue, trunk fat and lean body mass. In both studies, tesamorelin-treated patients completing the 26-week treatment period were re-randomized to blinded therapy with either daily placebo or a 2-mg dose of tesamorelin (1-mg/vial formulation) for an additional 26-week treatment period (extension phase) in order to assess maintenance of VAT reduction and to gather long-term safety data. For inclusion in the extension phase studies, participants must have completed the main phase with an FBG of no more than 150 mg/dL. 

Study 1 (ClinicalTrials.gov Identifier: NCT00123253) included 412 HIV-infected patients with lipodystrophy and excess abdominal fat to receive either a 2-mg dose of tesamorelin (1-mg/vial formulation) (n=273) or placebo (n=137). Study 2 (NCT00435136) included 404 HIV-infected patients with lipodystrophy and excess abdominal fat to receive either a 2-mg dose of tesamorelin (1-mg/vial formulation) (n=270) or placebo (n=126). 

Patients treated with tesamorelin for 52 weeks (T-T group) showed no change between weeks 26 and 52 in mean trunk fat (increase of 0.1 kg in Study 1 and decrease of 0.5 kg in Study 2, respectively, compared with an increase of 1.4 kg in patients in the placebo group in Study 1 and an increase of 1.09 kg in Study 2, respectively). There was also no change from week 26 baseline in mean lean body mass. 

“Central adiposity, characterized by the accumulation of excess visceral abdominal fat [EVAF], is a common complication for people with HIV that may result from the virus itself, from certain older antiretrovirals and from a reduction in growth hormone concentrations,” said David Alain Wohl, MD, a professor at the Institute of Global Health and Infectious Diseases, the University of North Carolina at Chapel Hill. “Given the significant impact of EVAF on health and quality of life for many of our patients with HIV, and the importance of maintaining lean muscle mass especially as we age, a new, more conveniently dosed formulation of tesamorelin is a welcome advancement.”

The long-term cardiovascular safety of tesamorelin has not been established. Consider risk/benefit of continuation of treatment in patients who have not seen a reduction in VAT. Tesamorelin is not indicated for weight-loss management because it does not affect weight. The full prescribing information is available here.

Tesamorelin will be supplied as four single-use vials, each containing 11.6 mg of tesamorelin, sufficient for seven doses. The daily dose is 1.28 mg (0.16 mL of the reconstituted solution) injected subcutaneously. The product can be stored at room temperature (20° to 25°C [68° to 77°F]) before and after reconstitution.