Initial safety and efficacy evaluation of the German pegvisomant observational study

Abstract

The recent approval of the first GH receptor antagonist Pegvisomant (Somavert®) has augmented the therapeutic armamentarium for the treatment of acromegaly. The limited longterm experience with this drug has prompted the need for systematic data capture and evaluation. Between Jan and end of Jul 2004, 102 pat. (52m, 50f) were enrolled pro- and retrospectively in a German Pegvisomant Observational Study. Mean pat. age was 47.5±13.1yrs. Mean age at diagnosis was 37.2yrs. 94% had previously undergone operation, 51% had received radiation therapy. Previous medical treatment comprised of dopamine agonists (54%) and/or somatostatin analogues (92%). Mean time of observation was 41.4wks. Efficacy analysis was performed in 71 pat. with an available follow-up investigation 23.4±14.8wks after baseline. Locally measured IGF-I at baseline was elevated in 86% of these pat.. During this early treatment phase with dose titration not escalated to normalize IGF-I in some, IGF-I declined to normal in 68% (mean dose 15.5mg/d, range 10–40mg/d). Elevated liver function tests (LFTs) occurred in 6/102 pat. 7–35wks after start of treatment, in 4 pat. >3x the upper limit of normal. In 4/6 pat., Pegvisomant was continued with spontaneous normalization of LFTs during follow-up in 2 cases. In 2 pat., levels normalized after treatment discontinuation. Progression of remnant pituitary adenoma was observed in 2 pat.. In both cases the slow and constant adenoma growth was documented to progress from before initiation of Pegvisomant and no change in growth rate was noted since Pegvisomant initiation. Lipohypertrophy at the injection site was noted in 3 pat. One pat. with uncontrolled disease for >20yrs and known preexisting cardiomyopathy has died. In conclusion, the Pegvisomant safety profile according to this initial evaluation is in agreement with the previously published experience. For the continued information about this new drug, this observational study should be carried forward and regularly be evaluated. *MB, MD, KM, and CJS on behalf of the German Pegvisomant Study Investigators.