Long-acting growth hormone preparations-current status and future considerations

Context: Long-acting GH (LAGH) preparations are currently being developed in an attempt toimprove adherence. The profile of GH action following administration of LAGH raises practicalquestions about clinical monitoring and long-term safety and efficacy of these new therapeuticagents.Methods: Recent literature and meeting proceedings regarding LAGH preparations arereviewed.Results: Multiple LAGH preparations are currently at various stages of development,allowing for decreased GH injection frequency from daily to weekly, biweekly, or monthly.Following administration of LAGH, the serum peak and trough GH and IGF-I levels varydepending upon the mechanism used to prolong GH action. Randomized, controlledclinical trials of some LAGH preparations have reported non-inferiority compared with dailyrecombinant human GH (rhGH) for improved growth velocity and body composition in childrenand adults with GH deficiency (GHD), respectively. No significant LAGH-related adverse eventshave been reported during short-term therapy.Conclusion: Multiple LAGH preparations are proceeding through clinical development withsome showing promising evidence of short-term clinical efficacy and safety in children and adultswith GHD. The relationship of transient elevations of GH and IGF-I following administrationof LAGH to efficacy and safety remain to be elucidated. For LAGH to replace daily rhGH inthe treatment of individuals with GHD, a number of practical questions need to be addressedincluding methods of dose adjustment, timing of monitoring of IGF-I, safety, efficacy, and costeffectiveness. Long-term surveillance of efficacy and safety of LAGH preparations will be neededto answer these clinically relevant questions.