Similar safety and efficacy in previously treated adults with growth hormone deficiency randomized to once‐weekly somapacitan or daily growth hormone

Otsuka, Fumio; Takahashi, Yutaka; Tahara, Shigeyuki; Ogawa, Yoshihisa; Rasmussen, Michael Højby; Takano, Koji

doi:10.1111/cen.14273

Cited by 25 publications

(36 citation statements)

References 22 publications

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“…The most frequent AE are injection site reaction and hyperpigmentation, followed by nausea and vomiting. A human growth hormone analog, somapacitan-beco (Otsuka et al 2020 ) was approved as a replacement therapy in patients with growth hormone deficiency. It is administered subcutaneously once a week, in contrast to previous therapies injected daily, thereby providing greater patient convenience.…”

Section: Neurologymentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020

Kaykı-Mutlu

Michel

2021

Naunyn-Schmiedeberg's Arch Pharmacol

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While the COVID-19 pandemic also affected the work of regulatory authorities, the US Food and Drug Administration approved a total of 53 new drugs in 2020, one of the highest numbers in the past decades. Most newly approved drugs related to oncology (34%) and neurology (15%). We discuss these new drugs by level of innovation they provide, i.e., first to treat a condition, first using a novel mechanisms of action, and “others.” Six drugs were first in indication, 15 first using a novel mechanism of action, and 32 other. This includes many drugs for the treatment of orphan indications and some for the treatment of tropical diseases previously neglected for commercial reasons. Small molecules continue to dominate new drug approvals, followed by antibodies. Of note, newly approved drugs also included small-interfering RNAs and antisense oligonucleotides. These data show that the trend for declines in drug discovery and development has clearly been broken.

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Section: Neurologymentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020

Kaykı-Mutlu

Michel

2021

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Somapacitan is a long-acting human GH derivative to which a small noncovalent albumin-binding moiety is attached to facilitate reversible binding to endogenous albumin, delaying its elimination, and thereby extending its duration of action with little to no accumulation of the drug when administered once-weekly ( 52 ). In previous short-term clinical trials, Somapacitan was well-tolerated in healthy adults ( 81 ) and in adults and children with GHD ( 53 , 54 , 82 ), and provided similar safety and efficacy to daily rhGH in previously rhGH-treated adults with GHD ( 54 , 55 ). In a Phase 3, 26-week randomized, controlled multi-center study of 92 adults with GHD treated with Somapacitan or daily Norditropin, Somapacitan was well-tolerated, IGF-I standard deviation scores remained in the therapeutic range, and patients preferred the weekly Somapacitan therapy ( 54 ).…”

Section: Long-acting Gh Analogs: Usefulness Mechanism/s and Current mentioning

confidence: 87%

Usefulness and Potential Pitfalls of Long-Acting Growth Hormone Analogs

et al. 2021

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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.

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“…Somapacitan PK and PK/PD models were based on data from patients with AGHD randomised to somapacitan (Sogroya ® , Novo Nordisk)) in three placebo- or active-controlled (somatropin (Norditropin ® NordiFlex ® , Novo Nordisk)) phase 3 trials (ClinicalTrials.gov identifiers: NCT02229851 (REAL 1), NCT02382939 (REAL 2), NCT03075644 (REAL JP) ( 13 , 14 , 15 )) ( Table 1 ).…”

Section: Methodsmentioning

confidence: 99%

“…REAL 2 and REAL JP enrolled patients were previously treated with human growth hormone (hGH). Further details on the trials, including eligibility criteria, were published previously ( 13 , 14 , 15 ).…”

Section: Methodsmentioning

confidence: 99%

Dose–exposure–IGF-I response of once-weekly somapacitan in adults with GH deficiency

Kildemoes

Hollensen

Johannsson

et al. 2022

European Journal of Endocrinology

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Objective: Growth hormone (GH) replacement therapy in patients with adult growth hormone deficiency (AGHD) is individually titrated due to variable dose–responses among patients. Our objective was to provide clinical guidance on dosing and titration of the novel long-acting GH derivative somapacitan based on analyses of somapacitan dose–insulin-like growth factor I (IGF-I) responses in AGHD patients. Design: Analyses of dosing information, 4364 somapacitan concentration samples and 4880 IGF-I samples from 330 AGHD patients treated with somapacitan in three phase 3 trials. Methods: Pharmacokinetic/pharmacodynamic modelling was used to evaluate starting dose groups by age and oral oestrogen therapy, characterise the dose–IGF-I response in the overall AGHD population and patient subgroups, predict the IGF-I response to dose changes and simulate missed dosing. Results: The analyses supported the clinical recommendations of higher starting doses for younger patients and women on oral oestrogen replacement therapy. For patients switching from daily GH treatment, the mean maintenance dose ratio between somapacitan (mg/week) and somatropin (mg/day) was predicted to be 8.2 (observed interquartile range of 6.7-9.1). Simulations of IGF-I SDS profiles confirmed the appropriate time for IGF-I sampling to be 3-4 days after somapacitan dosing, and supported somapacitan administration with up to 3 days delay in case of missed dosing. Subgroup analyses characterised the dose-exposure-IGF I response in patient subgroups and indicated that dose requirements are mainly influenced by sex and oral oestrogen treatment. Conclusions: This study extends knowledge of the somapacitan dose–IGF-I response and provides information on clinical dosing of once-weekly somapacitan in patients with AGHD.

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Similar safety and efficacy in previously treated adults with growth hormone deficiency randomized to once‐weekly somapacitan or daily growth hormone

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 25 publications

References 22 publications

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020

Usefulness and Potential Pitfalls of Long-Acting Growth Hormone Analogs

Dose–exposure–IGF-I response of once-weekly somapacitan in adults with GH deficiency

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