Long-acting growth hormone preparations and their use in children with growth hormone deficiency

Background: Daily recombinant human growth hormone (rhGH) is approved and marketed worldwide to treat children and adults with GH deficiency (GHD) and other conditions. Efficacy of rhGH therapy is influenced by several variables. Drop of treatment adherence over time has been recognized as a cause of reduced rhGH efficacy and has driven considerable efforts from pharmaceutical companies and scientists to develop long-acting rhGH (LAGH) formulations in order to relieve patients and their families from the burden of daily injections. Summary: Different technologies to manipulate drug release have been produced allowing weekly, biweekly or monthly rhGH administration. The LAGH formulations developed at present have demonstrated a comparable or even higher efficacy as compared with daily rhGH in most of the cases and no major safety issues in phase 3 studies. A greater incidence of injection-site reactions has been reported but mainly of mild and transient nature. Key messages: Despite LAGH analogs appearing promising, potential drawbacks still need to be addressed. Long-term consequences of un-physiological GH profile and its consequences on metabolism and risk of cancer, optimal therapeutic monitoring, immunogenicity of LAGH molecules and potential novel side-effects related to the technologies used to develop these molecules are among the major concerns that require answers from long-term surveillance. Finally, increased acceptance of LAGH formulations from patients and their caregivers is yet to be demonstrated and cost-effectiveness evaluated consequently.