Pegvisomant, a growth hormone receptor antagonist, has the potential to become a useful treatment for acromegaly, a new study has concluded. Pegvisomant blocks the effects of the excessive secretion of growth hormone that is seen in acromegaly. The secretion of growth hormone causes an increase in the production of insulin-like growth factor I (IGF-I) which pegvisomant prevents.
The efficacy and tolerability of pegvisomant were assessed by Dr Peter Trainer (Christie and South Manchester university hospitals) and colleagues in a 12-week trial. Three daily doses of pegvisomant (10, 15 and 20mg) were compared with placebo in the randomised, double-blind study of 112 patients.
In all three treatment groups, serum concentrations of IGF-I decreased (there was no change in the placebo group). The number of patients with normal IGF-I concentrations increased in a dose-dependent manner in the pegvisomant groups. The mean scores for individual symptoms and signs decreased in all pegvisomant groups, with significant decreases in scores for soft tissue swelling, excessive perspiration and fatigue. Ring sizes became smaller, showing a decrease in finger diameter, with larger reductions seen in patients taking higher doses of pegvisomant. The onset of action was rapid, with maximal reduction in IGF-I levels seen in 75 per cent of patients within two weeks of starting treatment.
In terms of safety, the drug was well tolerated, the authors report. The incidence of side effects was similar in all four study groups. However, serum growth hormone concentrations increased in the treatment groups. The authors comment that, while no effects on tumour growth were observed, a longer study of more patients is needed to examine this effect. The effects of pegvisomant on hepatic function and on the production of anti-growth hormone antibodies also need to be studied, they say.
Pegvisomant is highly selective for the growth hormone receptor and does not crossreact with other receptors, the authors say. They conclude that "treatment of patients who have acromegaly with a growth hormone receptor antagonist results in both a reduction in serum IGF-I concentrations and in clinical improvement" (New England Journal of Medicine 2000;342:1171).