Human mecasermin - A review of its use in amyotrophic lateral sclerosis

Human mecasermin (Myotrophin(R); somatomedin-1-cephalon-chiron; recombinant human insulin-like growth factor-I) is a growth factor with neurotrophic p roperties. In animal or in vitro studies, human mecasermin reduced naturally occurring or induced apoptosis of motoneurons and enhanced their survival or regrowt h. The efficacy of human mecasermin (50 and 100 mu g/kg/day subcutaneously) ha s been examined in 2 well designed, 9-month, placebo-controlled trials in 1 47 to 266 patients with mild to moderate sporadic amyotrophic lateral scler osis (ALS). In one trial, human mecasermin 100 mu g/kg/day, but not 50 mu g /kg/day, significantly slowed the progression of functional impairment, dis ease symptom progression and the deterioration in patients' quality of life when compared with placebo. However, this benefit was not confirmed in a s econd trial, in which human mecasermin 100 mu g/kg/day showed no greater ef ficacy than placebo in any parameter. Although these trials were not of sufficient size or duration to show a dir ect effect on mortality and results should be interpreted with caution, no significant differences were observed in mortality rate between human mecas ermin and placebo during the study period. However, in a long term follow-u p of I trial, a significant advantage in survival was apparent in patients who had received human mecasermin (100 mu g/kg/day) compared with placebo r ecipients when patients' age and lung function were accounted for. In clinical trials, human mecasermin was well tolerated, with injection sit e complaints being the most frequent adverse events. The incidence of most adverse events was generally similar to that with placebo except for inflam mation at the injection site, change in hair growth or texture, knee pain, facial oedema, lung disorder, sinusitis and joint swelling, which occurred significantly more frequently after human mecasermin (50 or 100 mu g/kg/day ). Conclusions: Data on the use of human mecasermin in patients with ALS are l imited and conflicting. Additional clinical trials, particularly comparison s with riluzole and possibly assessing the drug in combination with other a gents, will be useful to accurately determine the efficacy of human mecaser min in ALS. However, although the benefits of human mecasermin in ALS have not been conclusively proven, it is the first drug to show some evidence of being potentially able to slow disease symptom progression and the decline in patients' quality of life. In view of these findings, and also consider ing the limited choice of proven treatments currently available for this fa tal disease, human mecasermin should be considered as a treatment option in patients with ALS.