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Review
. 2021 Feb 24:12:637209.
doi: 10.3389/fendo.2021.637209. eCollection 2021.

Usefulness and Potential Pitfalls of Long-Acting Growth Hormone Analogs

Kevin C J Yuen  1 , Bradley S Miller  2 , Cesar L Boguszewski  3 , Andrew R Hoffman  4
Affiliations
Review

Usefulness and Potential Pitfalls of Long-Acting Growth Hormone Analogs

Kevin C J Yuen et al. Front Endocrinol (Lausanne). .

Erratum in

Abstract

Daily recombinant human GH (rhGH) is currently approved for use in children and adults with GH deficiency (GHD) in many countries with relatively few side-effects. Nevertheless, daily injections can be painful and distressing for some patients, often resulting in non-adherence and reduction of treatment outcomes. This has prompted the development of numerous long-acting GH (LAGH) analogs that allow for decreased injection frequency, ranging from weekly, bi-weekly to monthly. These LAGH analogs are attractive as they may theoretically offer increased patient acceptance, tolerability, and therapeutic flexibility. Conversely, there may also be pitfalls to these LAGH analogs, including an unphysiological GH profile and differing molecular structures that pose potential clinical issues in terms of dose initiation, therapeutic monitoring, incidence and duration of side-effects, and long-term safety. Furthermore, fluctuations of peak and trough serum GH and IGF-I levels and variations in therapeutic efficacy may depend on the technology used to prolong GH action. Previous studies of some LAGH analogs have demonstrated non-inferiority compared to daily rhGH in terms of increased growth velocity and improved body composition in children and adults with GHD, respectively, with no significant unanticipated adverse events. Currently, two LAGH analogs are marketed in Asia, one recently approved in the United States, another previously approved but not marketed in Europe, and several others proceeding through various stages of clinical development. Nevertheless, several practical questions still remain, including possible differences in dose initiation between naïve and switch-over patients, methodology of dose adjustment/s, timing of measuring serum IGF-I levels, safety, durability of efficacy and cost-effectiveness. Long-term surveillance of safety and efficacy of LAGH analogs are needed to answer these important questions.

Keywords: adults; children; growth hormone deficiency; growth hormone replacement; long-acting growth hormone; treatment adherence.

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Conflict of interest statement

KY is an investigator on research grants from Pfizer, Novo Nordisk, and OPKO Biologics, and has consulted for Pfizer, Novo Nordisk, Sandoz, and Ascendis. BM is an investigator on research grants from Alexion, Abbvie, Amgen, Ascendis, Novo Nordisk, OOKO Biologics, Protalix, Sangamo, Sanofi Genzyme, Tolmar, and Takeda and has consulted for Abbvie, Ascendis, BioMarin, Bluebird Bio, Novo Nordisk, Pfizer, Sandoz, Sanofi Genzyme, Tolmar, and Vertice. AH is supported by the Biomedical Research Service of the Department of Veterans Affairs and has consulted for Ascendis, GeneScience, Genexine, Novo Nordisk, Pfizer, and Versartis. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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