Tesamorelin—overview

In adults, growth hormone helps to maintain muscle mass and reduce the buildup of fatty tissues. Growth hormone is available by prescription but is very expensive and governments do not often subsidize the cost of this drug. HIV infection tends to reduce the body’s production of growth hormone, and some people have difficulty building up and maintaining muscle and they also develop fat deposited deep in the belly around organs. This type of fat is called visceral fat.

Background on an emerging therapy

Tesamorelin (Egrifta) is an analogue similar to the body’s growth-hormone-releasing factor; it causes the body to release growth hormone. Tesamorelin has been approved in the United States for the treatment of visceral fat accumulation in HIV-positive people.  In Canada and other countries, regulatory approval for tesamorelin is awaiting approval.

In placebo-controlled studies with more than 800 HIV-positive volunteers that lasted six months, daily injections (2 mg) of tesamorelin resulted in decreased visceral fat, reduced belly size and sometimes reduced levels of triglycerides in the blood. Next, we summarize the data used to seek approval for tesamorelin.

Tesamorelin—General side effects

Based on data from placebo-controlled phase III studies, some of the side effects reported are headache, joint pain and injection-site reactions. The distribution of some of these side effects was as follows:

Injection-site redness

• tesamorelin – 9%
• placebo – 3%

Joint stiffness and pain

• tesamorelin – 13%
• placebo – 11%

Muscle pain

• tesamorelin – 6%
• placebo – 2%

In general, the distribution of side effects did not differ because of age or gender.

Side effects related to injection-site reactions were most common; these included itchy rash, particularly on the abdomen where the drug was injected. Sometimes the rash occurred on other parts of the body.

A hypersensitivity reaction (HSR) occurred in 28 people (seven females and 21 males). In 41% of these 28 participants, researchers described the HSRs as “extended skin reactions” that affected other parts of the body. In these people with systemic HSRs, some or all of the following symptoms appeared:

• nausea
• rapid heart beats
• feeling dizzy or light-headed
• unexpected sweating
• unexpected shortness of breath
• headache

All symptoms resolved when participants were treated (with antihistamines and creams containing corticosteroids) and discontinued tesamorelin. Importantly, none of the HSRs became life threatening.

Cancer risk

In theory, there is a risk that use of tesamorelin—because it stimulates the release of growth hormone, which can drive the growth of cancer cells—may increase the risk for cancer. However, rates of cancer were low and similar among recipients of tesamorelin and placebo. Moreover, there was only one case of cancer among tesamorelin users where doctors suspected that this drug may have contributed to the growth of cancer (Hodgkin’s disease). A similar case of cancer also occurred in a person who received placebo.

Blood sugar

Some users of growth hormone have developed problems controlling their blood sugar levels. Tesamorelin has been tested in volunteers with diabetes and the drug did not make this condition worse.

In a small study with HIV-negative people without diabetes, there was a slight increase in the proportion of people whose average blood sugar levels over three months were slightly abnormal—2% among tesamorelin users vs. less than 1% among those taking placebo. But this difference, while statistically significant, was not clinically meaningful.

REFERENCE:

Theratechnologies. Tesamorelin (Egrifta). Briefing document. NDA 22-505. Endocrinologic and Metabolic Drugs. Food and Drug Administration Advisory Committee Meeting. May 27, 2010.