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Professor of Medicine
Department of Neuroendocrinology and Neurosurgery
Barrow Neurological Institute
Barrow Neuroendocrinology Clinic
Barrow Pituitary Center
Kevin C.J. Yuen, MD, FRCP (UK), FACE, has disclosed that he has received funds for research support from Amryt, Ascendis, Corcept, and Crinetics; consulting fees from Amryt, Ascendis, Corcept, Crinetics, Ipsen, Novo Nordisk, Recordati, and Strongbridge; and fees for non-CME/CE services from Corcept, Ipsen, and Novo Nordisk.
Growth hormone (GH) treatment currently is administered subcutaneously via daily injections, often from a pen device. However, maintaining treatment adherence with daily GH injections is challenging for children and their caregivers, as well as for adults with GH deficiency because of pain at injection sites, the inconvenience of daily injections, a lack of perceived immediate benefits, insurance barriers, and costs. This often leads to discontinuation of treatment. In response, long-acting GH preparations, which generally require only 1 injection per week, have been developed based on the hypothesis that reducing injection frequency would improve treatment adherence and patients’ quality of life.
Recent FDA Approvals
Two long-acting GH preparations recently have been approved by the FDA for the treatment of GH deficiency: lonapegsomatropin for pediatric patients and somapacitan for adult patients. Lonapegsomatropin was approved in August 2021, based on results from the phase III heiGHt trial that compared it with daily somatropin in 161 treatment-naive GH-deficient children. The study showed that lonapegsomatropin increased annualized height velocity—the primary endpoint—by 11.2 cm/year compared with 10.3 cm/year with daily somatropin (P = .009), demonstrating that lonapegsomatropin was superior to somatropin on this measure and was as safe as daily injections. Lonapegsomatropin is administered using an autoinjector and prefilled cartridges, which can be stored at room temperature.
Somapacitan was approved by the FDA based on a study of 301 adults with GH deficiency who had never received GH treatment or had stopped their daily GH injections at least 180 days before randomization. Patients were assigned either to receive weekly somapacitan, weekly placebo, or daily somatropin injections. This study showed that somapacitan improved body composition and other clinical endpoints compared with daily somatropin. However, somapacitan currently is not commercially available, and it is unclear when it will be available.
Patient selection is really the key to the success of this treatment. I would think that patients already on multiple injections, such as insulin, likely will find long-acting GH preparations to be beneficial. Patients who previously derived benefit from use of daily GH injections but do not like to self-inject daily and patients who are on daily GH injections but frequently miss their injections also could find long-acting GH preparations beneficial.
Like any new drug, there are many questions about long-acting GH preparations that can be answered only with increasing use and experience with the drug over time. Some questions include how to start and adjust dosing, when to best measure insulin-like growth factor-1 levels, whether the effects of the drug are sustainable over the long term, whether all long-acting GH preparations penetrate tissues equally given differences in molecular structure, and if these preparations will be associated with higher risk of developing complications like acromegaly and diabetes. Perhaps the 2 overarching questions that need to be answered soon are whether these drugs are cost-effective and if they will improve adherence and treatment outcomes.
Clearly, there is still much to be learned moving forward, but for now, the available data seem to suggest that long-acting GH preparations are a useful addition to available daily GH injections, especially for patients who are not coping well with the rigors of daily GH injections but are obtaining clear benefits from treatment and want to continue. Starting surveillance registries to collect data on efficacy, safety, and tolerability will help improve our understanding of the effects of prolonged exposure to these drugs.
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