Tesamorelin

A Growth Hormone-releasing Factor Analogue for HIV-associated Lipodystrophy

Linda M Spooner, PharmD BCPS; Jacqueline L Olin, MS PharmD BCPS CPP CDE

Disclosures

The Annals of Pharmacotherapy. 2012;46(2):240-247. 

In This Article

Abstract and Introduction

Abstract

Objective: To evaluate the efficacy and safety of tesamorelin, a growth hormone releasing factor analogue approved by the Food and Drug Administration in November 2010 for the treatment of lipodystrophy associated with HIV infection.
Data Sources: Literature was obtained through MEDLINE (1948-November 2011) and International Pharmaceutical Abstracts (1970-October 2011) using the search terms tesamorelin, TH9507, growth hormone releasing factor, and HIV-associated lipodystrophy syndrome. Additional publications were obtained through review of references within primary literature publications as well as pertinent Web sites.
Study Selection and Data Extraction: All articles published in English identified from the data sources were evaluated and all pertinent information was included. All studies relevant to the evaluation of efficacy and safety of tesamorelin in the management of HIV-associated lipodystrophy were included, with a focus on trials completed in humans.
Data Synthesis: In 2 Phase 3 clinical trials and their pooled analyses, tesamorelin was proven to significantly decrease waist circumference and visceral adipose tissue (VAT) following 26 weeks of treatment. Both trials also demonstrated significant improvements in some subjective body image parameters. Both studies had 26-week extension phases that confirmed maintenance of VAT improvements on treatment without adverse impact on blood glucose and lipid parameters. Limited data support off-label uses of tesamorelin at this time.
Conclusions: Tesamorelin is effective in improving visceral adiposity and body image in patients with HIV-associated lipodystrophy over 26–52 weeks of treatment. Potential limitations for its use include high cost and lack of long-term safety and adherence data. Tesamorelin provides a useful treatment option for management of patients with significant lipodystrophy related to HIV infection.

Introduction

Use of potent combination antiretroviral therapy (ART) for treatment of HIV infection has resulted in a substantial reduction in morbidity and mortality since its advent in the mid-1990s.[1] Since HIV infection is now a chronic, manageable disease, attention is often focused on longterm adverse effects associated with the infection and its management, including HIV-associated lipodystrophy. Lipodystrophy is characterized by loss of subcutaneous adipose tissue (SAT) in the face, extremities, and buttocks as well as accumulation of excess visceral adipose tissue (VAT) in the abdomen, dorsocervical region, trunk, and breasts.[2–4] VAT accumulation can be assessed via objective measurements (eg, dual-energy X-ray absorptiometry, computed tomography [CT] scanning) as well as via subjective report from the patient.[4] In addition to its psychosocial implications, including poor self-image and negative impact on adherence to ART, the accumulation of VAT is associated with insulin resistance and dyslipidemia, which increase the risk of diabetes mellitus and coronary artery disease.[5,6] Because of the lack of a standardized definition for HIV-associated lipodystrophy, prevalence rates vary from 11% to 83% in individuals receiving combination ART.[7] Interestingly, there is no relationship between specific ARTs and lipohypertrophy, and it is not recommended to change a patient's ART in an attempt to reduce fat accumulation.[3] Studies of exercise training programs in HIV-infected participants with lipodystrophy have had conflicting results, ranging from no impact on VAT to 12% VAT reduction.[3]

Numerous pathophysiologic mechanisms have been implicated in the development of lipodystrophy in HIV-in-fected individuals, including mitochondrial dysfunction caused by ART, dysregulation of fatty acid metabolism, abnormalities in adiponectin and leptin concentrations, alterations in glucocorticoid signaling, immune reconstitution, and impaired growth hormone secretion.[3] For this last pathophysiologic mechanism, recombinant human growth hormone has been studied and VAT reduction of 8.5–11% has been observed in clinical trials.[3] Recombinant human growth hormone has been approved by the Food and Drug Administration (FDA) for AIDS-related wasting; however, the doses required for the greatest reductions in VAT caused insulin resistance, arthralgias, carpal tunnel syndrome, and peripheral edema.[8] This resulted in the development of tesamorelin, an analogue of growth hormone releasing hormone (GHRH) that provides a different approach to the management of lipodystrophy in the HIV-infected individual.

Tesamorelin (Egrifta; manufactured by Theratechnologies Inc., Montreal, Quebec, Canada; distributed by EMD Serono, Rockland, MA) was approved by the FDA in November 2010 for the reduction of excess abdominal fat caused by HIV-associated lipodystrophy.[9] This article reviews the pharmacology, toxicology, pharmacokinetics, and pharmacodynamics of tesamorelin, as well as the clinical trial data assessing its use in the management of HIVassociated lipodystrophy. This article also discusses safety data, dosage and administration, and clinical perspectives related to tesamorelin use.

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