Pegvisomant (Somavert): how it works, uses and side effects

Pegvisomant is used for acromegaly when other treatments do not work well enough or are not suitable. It blocks the action of growth hormone at its receptors, which lowers the growth factor IGF-1. It does not shrink the underlying tumor of the pituitary gland. For that reason, the size of the tumor has to be checked regularly with imaging during treatment.

What is pegvisomant?

Pegvisomant is sold under the brand name Somavert. It is a genetically engineered variant of human growth hormone that has been chemically modified and linked to polyethylene glycol (PEG). It acts at a different point from somatostatin analogs: those lower the release of growth hormone from the pituitary, whereas pegvisomant blocks the hormone’s action at its target cells. It prevents the hormone from triggering a signal through its receptor.

Pegvisomant was developed from a modified growth hormone molecule called B2036. It was approved in the United States in 2003.

How does pegvisomant work?

For growth hormone to trigger a signal, two subunits of its receptor have to work together. Pegvisomant binds to this receptor, but its altered molecular structure stops the receptor from taking on the shape needed to pass the signal on. In this way it blocks the interplay between the subunits. As a result, the liver produces less insulin-like growth factor 1 (IGF-1). This growth factor is linked to disease activity in acromegaly; when its level falls, symptoms can improve.

Pegvisomant acts at the receptors in the body. It does not reduce the release of growth hormone by the pituitary tumor. Measured growth hormone levels can therefore even rise while IGF-1 returns to normal. PEG extends the drug’s half-life, the time it takes for the amount in the body to fall by half. This makes once-daily dosing possible.

In a controlled study, IGF-1 levels returned to normal in about 90% of those treated with 20 mg of pegvisomant daily. Their symptoms also improved.

Is pegvisomant FDA-approved?

Yes. The US Food and Drug Administration (FDA) approved pegvisomant in 2003 for the treatment of acromegaly. The drug is injected daily subcutaneously, that is, under the skin. Treatment usually starts with a loading dose. This is followed by a daily maintenance dose that is adjusted step by step based on IGF-1 levels. Details on use are given in the US prescribing information.

For more on the growth factor itself, see the article on IGF-1 and longevity.

What is pegvisomant prescribed for?

Pegvisomant is an option for people with acromegaly whose condition has not responded well enough to surgery, radiation or other medicines. It is also used when those treatments are not suitable. Because pegvisomant lowers IGF-1 but does not shrink the tumor, regular imaging of the pituitary gland is still needed.

What are the side effects?

The US prescribing information lists the following among its common side effects:

• Injection site reactions, including lumpy buildup of fatty tissue (lipohypertrophy)
• Infections, for example with cold symptoms
• Pain
• Nausea and diarrhea
• Flu-like symptoms
• Abnormal liver test results

Some risks need particular attention. The course of the disease also has to be monitored:

• Raised liver enzymes and, rarely, liver damage: liver values are therefore monitored during treatment.
• Low blood sugar in people with diabetes: their diabetes medicines may need to be adjusted.
• Tumor size: this has to be checked over the course of treatment, because pegvisomant does not shrink the tumor.