The Use of IGF-I to Monitor Long-Acting Growth Hormone Therapy—Timing is an Art…

Bidlingmaier, Martin; Schilbach, Katharina

doi:10.1210/clinem/dgab016

Cited by 12 publications

(12 citation statements)

References 7 publications

(11 reference statements)

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“…With daily administered rhGH products, the time of sample collection for IGF-1 measurement is not a concern, as fluctuations over the 24-hour dosing interval are modest and as such, all sampling times provide reasonable estimates of the average IGF-1 SDS. However, as noted previously ( 26 ) and highlighted by Bidlingmaier ( 30 ), interpretation of IGF-1 SDS for somatrogon needs to consider the timing of sample collection due to the significant peak trough fluctuation over the dosing interval. With weekly dosing of long-acting somatrogon, samples collected 2 or 3 days after the dose provide good estimates of peak IGF-1.…”

Section: Discussionmentioning

confidence: 85%

“…With weekly dosing of long-acting somatrogon, samples collected 2 or 3 days after the dose provide good estimates of peak IGF-1. Although collecting samples approximately 96 hours (4 days) post somatrogon dose will provide an accurate estimate of the mean IGF-1 SDS over the dosing interval, in real-world practice, IGF-1 SDS monitoring at any day after dosing will require the use of PK/PD-generated models for all long-acting GH products ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

“…Other strengths of this study include the diversity of subjects (21 countries), the examination of adherence, and the fact that the range of peak GH values in this study reflect those seen in a clinical setting. The potential weaknesses of the study include the difficulty of knowing what constitutes a safe and optimal level of IGF-1 and the lack of long-term safety and efficacy data on long-acting GH preparations ( 30 , 31 ). However, the latter is currently being addressed in the OLE period of this study as well as the OLE of the phase 2 study ( 20 ) of somatrogon mentioned previously.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study

Deal

Steelman

Vlachopapadopoulou

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Somatrogon is a long-acting recombinant human growth hormone (rhGH) in development for once-weekly treatment of children with growth hormone deficiency (GHD). Objective Compare the efficacy and safety of once-weekly somatrogon with once-daily somatropin in prepubertal children with GHD. Design 12-month, open-label, randomized, active-controlled, parallel-group, phase 3 study. Intervention Subjects were randomized 1:1 to receive once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. Patients or Other Participants 228 prepubertal children (boys aged 3-11 years, girls aged 3-10 years) with GHD, impaired height and height velocity (HV), and no prior rhGH treatment were randomized and 224 received ≥1 dose of study treatment (somatrogon: 109; somatropin: 115). Main Outcome Measures The primary endpoint was annualized HV at month 12. Results HV at month 12 was 10.10 cm/year for somatrogon-treated subjects and 9.78 cm/year for somatropin-treated subjects, with a treatment difference (somatrogon-somatropin) of 0.33 (95% CI: –0.24, 0.89). The lower bound of the two-sided 95% confidence interval was higher than the prespecified non-inferiority margin (–1.8 cm/year), demonstrating non-inferiority of once-weekly somatrogon vs daily somatropin. HV at month 6 and change in height SDS at months 6 and 12 were similar between both treatment groups. Both treatments were well tolerated, with a similar percentage of subjects experiencing mild to moderate treatment-emergent adverse events in both groups (somatrogon:78.9%, somatropin:79.1%). Conclusions The efficacy of once-weekly somatrogon was non-inferior to once-daily somatropin, with similar safety and tolerability profiles.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study

Deal

Steelman

Vlachopapadopoulou

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…With daily GH, stable IGF-I levels are achieved within days to weeks of starting on a new dose ( 38 ). Following injection of long-acting GH, there is an increase in IGF-I concentrations over a few days, reaching a maximum that may exceed the usual defined normal reference range, before declining to trough concentrations prior to the next injection ( 39 ). The reported IGF-I SDS value therefore depends on the time of sampling, as the maximum levels are higher, and the trough values are lower with long-acting GH than those with daily GH.…”

Section: Discussionmentioning

confidence: 99%

Effective GH Replacement With Once-weekly Somapacitan vs Daily GH in Children with GHD: 3-year Results From REAL 3

Sävendahl

Battelino

Rasmussen

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Current GH therapy requires daily injections, which can be burdensome. Somapacitan is a long-acting GH derivative in development for treatment of GH deficiency (GHD). Objective Evaluate the efficacy, safety, and tolerability of once-weekly somapacitan after 3 years of treatment. Design A multicenter, randomized, controlled, phase 2 study comparing somapacitan and once-daily GH for 156 weeks (NCT02616562). Setting Twenty-nine sites in 11 countries. Patients Fifty-nine children with GHD randomized (1:1:1:1) and exposed to treatment. Fifty-three children completed the 3-year period. Interventions Patients received somapacitan (0.04 [n=14], 0.08 [n=15] or 0.16 [n=14] mg/kg/week) or daily GH (n=14) (0.034 mg/kg/day, equivalent to 0.238 mg/kg/week) subcutaneously during the first year, after which all patients on somapacitan received 0.16 mg/kg/week. Main Outcome Measures Height velocity (HV) at year 3; changes from baseline in height standard deviation score (HSDS), HVSDS and IGF-I SDS. Results The estimated treatment difference (95% CI) in HV for somapacitan 0.16/0.16 mg/kg/week versus daily GH at year 3 was 0.8 cm/year (−0.4; 2.1). Change in HVSDS from baseline to year 3 was comparable between somapacitan 0.16/0.16 mg/kg/week, the pooled somapacitan groups, and daily GH. A gradual increase in HSDS from baseline was observed for all groups. At year 3, mean HSDS was similar for the pooled somapacitan groups and daily GH. Change from baseline to year 3 in mean IGF-I SDS was similar across treatments. Conclusions Once-weekly somapacitan in children with GHD showed sustained efficacy over 3 years in all assessed height-based outcomes with similar safety and tolerability to daily GH.

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“…Additionally, since IGF-I values are not normally distributed, the SDS values may vary by age and assay. 26 For this reason, further validation of the model with different IGF-I assays are needed.…”

Section: Introductionmentioning

confidence: 99%

Spotlight on Lonapegsomatropin Once-Weekly Injection and Its Potential in the Treatment of Growth Hormone Deficiency in Pediatric Patients

Miller¹,

Yuen²

2022

DDDT

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Lonapegsomatropin, a long-acting GH therapy (LAGH), was approved by the United States Food and Drug Administration in August 2021 for the treatment of pediatric growth hormone deficiency (GHD). Lonapegsomatropin is a prodrug consisting of unmodified GH transiently conjugated to methoxypolyethylene glycol which enables time-release of GH with a half-life of ~25 hours allowing for onceweekly administration. Clinical trials of lonapegsomatropin have demonstrated positive efficacy results in children (phase 2 and 3) and adults (phase 2) with GHD. The phase 3 trial in children with GHD established non-inferiority and statistical superiority of height velocity with lonapegsomatropin (11.2 cm/yr) compared to daily GH (10.3 cm/yr), with no concerning side effects with lonapegsomatropin. Similar growth responses have been reported in other LAGH products in phase 2 (somapacitan) and phase 3 (somatrogon) trials. Lonapegsomatropin is distributed in temperature-stable, prefilled cartridges at 9 different doses that can be prescribed based upon specific weight brackets designed to deliver approximately 0.24 mg/kg/wk. An electronic delivery device is required to combine the powdered medication with the diluent and deliver the medication subcutaneously through a small gauge needle to the recipient. The pharmacodynamic data from the clinical trials of lonapegsomatropin has been used to develop models to estimate an average IGF-1 value drawn at any time during the weekly injection interval. This average IGF-1 value may be used to for safety monitoring and/or to guide dose adjustment. New LAGH products, including lonapegsomatropin, may potentially improve patient adherence, quality of life and clinical outcomes, particularly in patients with poor adherence to daily GH injections in the future. With the availability of new LAGH products, clinicians will need to identify the best candidates for LAGH therapy and understand how to monitor and adjust therapy. Long-term surveillance studies are needed to demonstrate adherence, efficacy, cost-effectiveness and safety of LAGH preparations.

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The Use of IGF-I to Monitor Long-Acting Growth Hormone Therapy—Timing is an Art…

Cited by 12 publications

References 7 publications

Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study

Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study

Effective GH Replacement With Once-weekly Somapacitan vs Daily GH in Children with GHD: 3-year Results From REAL 3

Spotlight on Lonapegsomatropin Once-Weekly Injection and Its Potential in the Treatment of Growth Hormone Deficiency in Pediatric Patients

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