scholarly journals LUM-201 Elicits Greater GH Response than Standard GH Secretagogues in Pediatric Growth Hormone Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A679-A680
Author(s):  
George Bright ◽  
Roy Smith ◽  
Michael O Thorner
Keyword(s):  
Single Dose ◽  
Bone Age ◽  
Interquartile Range ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Gh Secretagogues ◽  
Moderate Growth ◽  
Igf I ◽  
Stimulation Tests ◽  
The Difference

Abstract Presentation Type: OralScience Type and Topic: Clinical Trial Introduction: LUM-201 (ibutamoren, formerly MK-0677) is an orally administered GH-secretagogue that stimulates the GH secretagogue receptor (GHSR1a) in the hypothalamus and pituitary. LUM-201 is in development for long-term use in a subset of PGHD patients with moderate growth deficiencies. A diagnosis of PGHD is confirmed by low GH responses to standard GH secretagogues (clonidine, arginine, L-dopa, glucagon, insulin) so it is somewhat counter-intuitive to suggest that children who cannot respond to one GH secretagogue might have favorable responses to LUM-201. Objective: To determine if LUM-201 stimulates GH responses differently than standard GH secretagogues. Methods: 68 naïve-to-treatment, prepubertal children with GHD received two standard GH stimulation tests and a test with a single 0.8 mg/kg dose of LUM-201. The 68 subjects included 20 girls and 48 boys. The median (interquartile range) age was 9.2 years (7.2,10.8), bone age 6.0 years (4.5, 7.9), height SDS -3.3 (-4.5, -2.5), pretreatment height velocity 4.0 cm/y (3.2, 4.6), and baseline IGF-1 51 ng/mL (24,111). Results: The median (interquartile range) of maximal GH response to single dose LUM-201 was 15.0 ng/mL (3.5, 49) and to various pairs of standard stimuli was 5.4 ng/mL (1.8-7.6) (p< 0.00001). The median (IQR) for the difference between GH responses to LUM-201 and standard stimuli was 9.6 ng/ml (1.9, 42). In a multivariate analysis (r2 =0.73) differential GH increased with higher values of baseline IGF-I (p < 0.00001) and standard GH stimulation test (p = 0.047) but was not influenced by age (p = 0.16), sex (p = 0.28), baseline HV (p = 0.24), age-bone age differences (p = 0.33) or height-SDS (p = 0.75). Conclusion: In GHD children, the GH response to single dose LUM-201 greatly exceeds that observed with standard GH testing agents. The difference is greatest among patients with higher baseline values of IGF-I and higher GH responses to standard stimuli. The synergistic actions of LUM-201 on the physiological mechanisms regulating GH release explain why GH responses are greater in response to LUM-201 compared to traditional tests used to diagnose PGHD. Key words: LUM-201, GH deficiency, GH secretagogues, pediatrics, stimulation tests, short stature, pituitary, hypothalamus

scholarly journals Can exaggerated response to a GH provocative test identify patients with partial GH insensitivity syndrome?

2002 ◽  
pp. 319-323 ◽  
Author(s):  
Y Rakover ◽  
A Silbergeld ◽  
I Lavi ◽  
R Masalha ◽  
IB Shlomo
Keyword(s):  
Short Stature ◽  
Binding Protein ◽  
Standard Deviation Score ◽  
Bone Age ◽  
The Other ◽  
Provocative Test ◽  
Igf I ◽  
Parental Height ◽  
The Difference ◽  
Igfbp 3

OBJECTIVES: In the majority of children with short stature, the etiology is unknown. Mutations of the GH receptor (GHR) have been reported in a few children with apparent idiopathic short stature (ISS). These patients had low IGF-I, IGF-binding protein-3 (IGFBP-3) and GH-binding protein (GHBP), but a normal or exaggerated GH response to provocative stimuli, suggestive of partial GH insensitivity (GHI). We attempted to identify children with partial GHI syndrome, based on their response to GH provocative stimuli and other parameters of the GH-IGF-I axis. SUBJECTS AND METHODS: One hundred and sixty-four pre-pubertal children (97 boys, 67 girls) aged 7.2 (0.5-16.75) years were studied. All had short stature with height <3rd centile. The weight, bone age (BA) and body mass index (BMI) of the subjects, as well as the parents' heights and mid parental height (MPH) were assessed. Basal blood samples were taken for IGF-I, IGFBP-3 and GHBP. All subjects underwent a GH provocative test with either clonidine, arginine or insulin. The subjects were divided into three groups: (A) patients with peak GH concentration <18 mIU/l in two different provocative tests (GH deficiency - GHD, n=33); (B) patients with peak GH between 18.2 and 39.8 mIU/l (normal response, n=78); (C) patients with peak GH >40 mIU/l (exaggerated GH response, n=53). RESULTS: No significant differences were found in age, height (standard deviation score (SDS)), parental height (SDS) and the difference between chronological age and bone age (DeltaBA) between the groups. Patients with GHD were heavier (P=0.039) and had significantly higher BMI (SDS) (P=0.001) than the other groups. MPH (SDS) was lower in the group of exaggerated responders (P=0.04) compared with the other groups. No significant differences were found between the groups for the biochemical parameters when expressed nominally or in SDS, except for IGFBP-3 (SDS), which was lower in the GHD group (P=0.005). The GHBP levels were not lower in the group of exaggerated GH response to provocative stimuli. Height (SDS) correlated negatively with basal GH values in pooled data of all the subjects (r=-0.358, P<0.0001), in normal responders (r=-0.45, P<0.0001) and in the exaggerated responders (r=-0.341, P<0.0001), but not in the GHD group. CONCLUSION: Exaggerated GH response to provocative tests alone does not appear to be useful in identifying children with GHI.

Transient impairment or delay of urinary trihydroxypregnanone (THS) response to metyrapone in boys with delayed adolescence and in patients with isolated growth hormone deficiency

1982 ◽  
Vol 99 (2) ◽  
pp. 166-173 ◽  
Author(s):  
M. Zachmann ◽  
D. Tassinari ◽  
W. Sorgo ◽  
G. U. Exner ◽  
B. Kempken ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Single Dose ◽  
Growth Hormone Deficiency ◽  
Bone Age ◽  
Urine Samples ◽  
Hormone Deficiency ◽  
Cortisol Response ◽  
Transient Impairment ◽  
Group A ◽  
Group B

Abstract. Twentythree boys with delayed adolescence (age 15.7 ± 2.0, bone age 12.4 ± 2.1 years) were studied. Their cortisol response to insulin was normal. After oral metyrapone (500 mg/m2 by mouth) one to three consecutive 12 h urine samples were collected for analysis of THS. Thirtyseven tests with 37 first, 21 second, and 11 third samples were carried out. The results could be divided into two main groups: 25 tests (group A) were subnormal in the first sample, 12 of them with a very weak (40 ± 8 μg/m2/12 h) and 13 with an insufficient (191 ± 16 μg/m2/12 h) THS response. Values in the second and third sample were higher, indicating a dealyed response. In 12 tests (group B), the results were normal (1016 ± 143 μg/m2/12 h) in the first and lower in the second and third samples. In three patients with repeated tests, there was improvement with increasing bone age. The THS-responses to metyrapone did not correlate with those of growth hormone, gonadotrophins, and TSH to stimuli. It is concluded that the THS-response to a single dose of metyrapone may be temporarily insufficient or delayed in delayed adolescence. We interpret this finding as showing transiently reduced or slow hypothalamic responsiveness.

Insulin-like growth factor ternary complex components as biomarkers for the diagnosis of short stature

2021 ◽  
Vol 185 (5) ◽  
pp. 629-635
Author(s):  
Aristeidis Giannakopoulos ◽  
Alexandra Efthymiadou ◽  
Dionisios Chrysis
Keyword(s):  
Growth Factor ◽  
Short Stature ◽  
Ternary Complex ◽  
Final Height ◽  
Hormone Deficiency ◽  
Receiver Operating Curve ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Stimulation Tests ◽  
Igfbp 3

Objective The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because insulin-like growth factor 1 (IGF-I) or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature. Design Boys and girls (n = 429, 0.7–16 years) who attended our department for short stature participated in this study. They were followed up for an average period of 9 years. At the end of follow-up after reaching the final height, a definitive diagnosis was assigned, and all the components of ternary complex (IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and IGF-I/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis. Results All the components of the ternary complex were tightly correlated with each other and were positively related to age. IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-I and ALS levels were lower in GHD compared to children with familial short stature, while IGF-I and IGF-I/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-I and IGF-I/IGFBP-3 receiver operating curve cutoff points were unable to discriminate between GHD and normal groups or between GHD and CDGP groups. Conclusion Despite the tight correlation among all the components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-I, ALS, and IGF-I/IGFBP-3 ratio in the distinction between GHD and CDGP or between GHD and normal groups but without usable discriminating power, making auxology as the primary criterion for establishing the diagnosis.

scholarly journals Significance of Direct Confirmation of Growth Hormone Insensitivity for the Diagnosis of Primary IGF-I Deficiency

2020 ◽  
Vol 9 (1) ◽  
pp. 240
Author(s):  
Joanna Smyczyńska ◽  
Urszula Smyczyńska ◽  
Maciej Hilczer ◽  
Renata Stawerska ◽  
Andrzej Lewiński
Keyword(s):  
Growth Hormone ◽  
Final Height ◽  
Standard Deviation Score ◽  
Height Velocity ◽  
Gh Therapy ◽  
Significant Difference ◽  
Igf I ◽  
Growth Hormone Insensitivity ◽  
Stimulation Tests ◽  
Direct Confirmation

Primary insulin-like growth factor-I (IGF-I) deficiency is a synonym of growth hormone (GH) insensitivity (GHI), however the necessity of direct confirmation of GH resistance by IGF-I generation test (IGF-GT) is discussed. GHI may disturb intrauterine growth, nevertheless short children born small for gestational age (SGA) are treated with GH. We tested the hypothesis that children with appropriate birth size (AGA), height standard deviation score (SDS) <−3.0, GH peak in stimulation tests (stimGH) ≥10.0 µg/L, IGF-I <2.5 centile, and excluded GHI may benefit during GH therapy. The analysis comprised 21 AGA children compared with 6 SGA and 20 GH-deficient ones, with height SDS and IGF-I as in the studied group. All patients were treated with GH up to final height (FH). Height velocity, IGF-I, and IGF binding protein-3 (IGFBP-3) concentrations before and during first year of treatment were assessed. Effectiveness of therapy was better in GHD than in IGF-I deficiency (IGFD), with no significant difference between SGA and AGA groups. All but two AGA children responded well to GH. Pretreatment IGF-I and increase of height velocity (HV) during therapy but not the result of IGF-GT correlated with FH. As most AGA children with apparent severe IGFD benefit during GH therapy, direct confirmation of GHI seems necessary to diagnose true primary IGFD in them.

scholarly journals Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence

2015 ◽  
Vol 101 (1) ◽  
pp. 96-100 ◽  
Author(s):  
P G Murray ◽  
M T Dattani ◽  
P E Clayton
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Childhood And Adolescence ◽  
Supporting Evidence ◽  
Diagnosis And Management ◽  
False Positive Diagnosis ◽  
Starting Dose ◽  
Igf I ◽  
Stimulation Tests

Growth hormone deficiency (GHD) is a rare but important cause of short stature in childhood with a prevalence of 1 in 4000. The diagnosis is currently based on an assessment of auxology along with supporting evidence from biochemical and neuroradiological studies. There are significant controversies in the diagnosis and management of GHD. Growth hormone (GH) stimulation tests continue to play a key role in GHD diagnosis but the measured GH concentration can vary significantly with stimulation test and GH assay used, creating difficulties for diagnostic accuracy. Such issues along with the use of adjunct biochemical markers such as IGF-I and IGFBP-3 for the diagnosis of GHD, will be discussed in this review. Additionally, the treatment of GHD remains a source of much debate; there is no consensus on the best mechanism for determining the starting dose of GH in patients with GHD. Weight and prediction based models will be discussed along with different mechanisms for dose adjustment during treatment (auxology or IGF-I targeting approaches). At the end of growth and childhood treatment, many subjects diagnosed with isolated GHD re-test normal. It is not clear if this represents a form of transient GHD or a false positive diagnosis during childhood. Given the difficulties inherent in the diagnosis of GHD, an early reassessment of the diagnosis in those who respond poorly to GH is to be recommended.

scholarly journals Once-Weekly Somapacitan vs Daily GH in Children With GH Deficiency: Results From a Randomized Phase 2 Trial

2020 ◽  
Vol 105 (4) ◽  
pp. e1847-e1861 ◽  
Author(s):  
Lars Sävendahl ◽  
Tadej Battelino ◽  
Meryl Brod ◽  
Michael Højby Rasmussen ◽  
Reiko Horikawa ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Phase 2 ◽  
Gh Treatment ◽  
Double Blind ◽  
Daily Growth ◽  
Phase 2 Trial ◽  
Igf I ◽  
Treatment Naïve

Abstract Context Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly administration in patients with growth hormone deficiency (GHD). Objective The objective of this study is to evaluate the efficacy, safety, and tolerability of once-weekly somapacitan vs once-daily GH. Design REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562). Setting This study took place at 29 sites in 11 countries. Patients Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial. Interventions Interventions comprised 3 somapacitan doses (0.04 [n = 16], 0.08 [n = 15], or 0.16 mg/kg/wk [n = 14]) and daily GH (0.034 mg/kg/d [n = 14]), administered subcutaneously. Main Outcome Measures The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS. Results At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week—daily GH): 1.7 [95% CI –0.2 to 3.6] cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was −1.62 (0.86), −1.09 (0.78), and 0.31 (1.06), respectively, vs −0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH. Conclusions In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).

scholarly journals Recommended IGF-I Dosage Causes Greater Fat Accumulation and Osseous Maturation Than Lower Dosage and May Compromise Long-term Growth Effects

2013 ◽  
Vol 98 (2) ◽  
pp. 839-845 ◽  
Author(s):  
Jaime Guevara-Aguirre ◽  
Arlan L. Rosenbloom ◽  
Marco Guevara-Aguirre ◽  
Jannette Saavedra ◽  
Patricio Procel
Keyword(s):  
Growth Promotion ◽  
Receptor Gene ◽  
Splice Site Mutation ◽  
Bone Age ◽  
Abdominal Ultrasound ◽  
Height Velocity ◽  
High Dose ◽  
Site Mutation ◽  
Percentage Body Fat ◽  
Igf I

Abstract Context: The maximum dose of IGF-I recommended for treatment of GH insensitivity is commonly used. Objective: The aim was to test the hypothesis that a lower dose is as effective as a high dose of IGF-I in growth promotion and has fewer deleterious effects. Design and Setting: Subjects were treated for 3 years with regular examinations including bone age and dual energy x-ray absorptiometry and for 1 year with abdominal ultrasound studies at a clinical research institute in Quito, Ecuador. Subjects: The study included 21 subjects ages 3.2–15.9 years with GH insensitivity due to the same splice site mutation on the GH receptor gene. Interventions: Subjects were allocated to receive 120 (n = 14) or 80 (n = 7) μg/kg IGF-I twice daily. Main Outcome Measures: Height velocity, osseous maturation, height SD scores (SDS), body composition, abdominal organ growth, and side effects were assessed. Results: There were no differences in growth velocity or height SDS increment by dosage, and the SDS increase was greater than in other reported series. Osseous maturation over 3 years with the high dose was nearly twice as rapid as with the lower dose (P &lt; .001) and correlated with an increase in percentage body fat (r = .64; P &lt; .001) and with adrenal size increase over 1 year (r = .32; P = .03). The ratio of bone age to height age was lower in the high-dose group after 3 years of treatment (P = .007). Conclusions: The commonly used IGF-I dosage of 120 μg/kg twice a day is excessive in comparison to a dose of 80 μg/kg twice a day, disproportionately accelerating osseous maturation, probably from the combined effects of obesity and inappropriate adrenal growth, thus likely compromising adult height potential. Moreover, the lower dose decreases direct treatment cost by one-third.

scholarly journals A new and accurate prediction model for growth response to growth hormone treatment in children with growth hormone deficiency

2001 ◽  
pp. 13-20 ◽  
Author(s):  
E Schonau ◽  
F Westermann ◽  
F Rauch ◽  
A Stabrey ◽  
G Wassmer ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Prediction Model ◽  
Growth Response ◽  
Prediction Models ◽  
Bone Age ◽  
Individual Growth ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Therapeutic Success ◽  
Rhgh Therapy

OBJECTIVE: To identify parameters which predict individual growth response to recombinant human GH (rhGH) therapy and to combine these parameters in a prediction model. DESIGN: Fifty-eight prepubertal patients with GH deficiency (17 females) participated in this prospective multicenter trial with 1 year of follow-up. METHODS: Auxological measurements, parameters of GH status and markers of bone metabolism were measured at baseline and at 1, 3 and 6 months after the start of rhGH treatment. Correlations with height velocity during the first 12 months of treatment (HV+12) were calculated. Prediction models were derived by multiple regression analysis. RESULTS: The model which best predicted HV+12 combined the following parameters: pretreatment bone age retardation as a fraction of chronological age, pretreatment serum levels of IGF-I, urinary levels of deoxypyridinoline (a marker of bone resorption) after 1 month of treatment and height velocity after 3 months of treatment. This model explained 89% of the variation in HV+12 with a standard deviation of the residuals of 0.93 cm/year. Defining successful rhGH therapy as a doubling of pretreatment height velocity, the model had a specificity of 90% and a sensitivity of 100% in predicting therapeutic success. CONCLUSIONS: This model is an accurate and practicable tool to predict growth response in GH-deficient children. It may help to optimize rhGH therapy by individual dose adjustment and contribute to improved overall outcomes.

Review of Turkish patients with growth hormone insensitivity (Laron type)

1995 ◽  
Vol 133 (5) ◽  
pp. 539-542 ◽  
Author(s):  
Nurşen Yordam ◽  
Nurgün Kandemir ◽  
Ibrahim Erkul ◽  
Selim Kurdoğlu ◽  
Şükrü Hatun
Keyword(s):  
Growth Hormone ◽  
Standard Deviation Score ◽  
Bone Age ◽  
High Rate ◽  
Hormone Deficiency ◽  
Turkish Children ◽  
Number Of Patients ◽  
Igf I ◽  
Growth Hormone Insensitivity ◽  
Turkish Patients

Yordam N, Kandemir N, Erkul I, Kurdoğlu S, Hatun S. Review of Turkish patients with growth hormone insensitivity (Laron type). Eur J Endocrinol 1995;133:539–42. ISSN 0804–4643 Clinical spectrum and endocrine details of thirteen Turkish children (age 0.3–14.2 years; eight females and five males; ten prepubertal, three pubertal) with growth hormone insensitivity are presented. All patients display phenotypical features of severe growth hormone deficiency, The diagnosis based on height standard deviation score (SDS), basal growth hormone (GH), basal insulin-like growth factor I (IGF-I, IGF-I response in an IGF generation test and growth hormone binding protein (GHBP) measurements. The median height SDS was −7.4 (range −3.2 to −10), weight for height index was 100 (range 81–152) and bone age/height age ratio was 2 (range 1.6–3.3). Endocrine investigations showed a median basal GH concentration of 61.4 mU/l (range 23.5–120 mU/l), Basal IGF-I level was below 10 ng/ml in all patients except one. None of the patients showed a significant IGF-I response to injections of GH (0.1 U/kg body weight for 4 days). The median IGFBP-3 level was 0.23 mg/l (range 0.1–0.56 mg/l). The GHBP level was undetectable in all of 10 patients. The high number of patients in our center may be due to the high rate of consanguinity among the Turkish population and the referral facility of our center in the area. These patients may benefit from the new therapy with recombinant human IGF-I. Nurgün Kandemir, Hacettepe University, Department of Pediatrics, Division of Endocrinology, 06100 Ankara, Turkey

scholarly journals Efficacy and Safety of up to 2 Years of Treatment With TransCon hGH (Lonapegsomatropin) in Treatment-Naïve and Treatment-Experienced Children With Growth Hormone Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A676-A676
Author(s):  
Aristides K Maniatis ◽  
Samuel J Casella ◽  
Ulhas M Nadgir ◽  
Paul Hofman ◽  
Paul Saenger ◽  
...  
Keyword(s):  
Safety Profile ◽  
Bone Age ◽  
Ease Of Use ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Weekly Dose ◽  
Open Label ◽  
Post Dose ◽  
Treatment Naïve ◽  
Auto Injector

Abstract Background: Once-weekly TransCon hGH (lonapegsomatropin) is an investigational long-acting prodrug of somatropin in development for GHD. In the pivotal 52-week phase 3 heiGHt trial, lonapegsomatropin demonstrated superior annualized height velocity (AHV) compared to the same weekly dose of daily somatropin in treatment-naïve children with GHD. In the 26-week fliGHt trial, switch from daily somatropin to lonapegsomatropin provided continued growth and maintained a good safety profile. Methods: Results are reported from heiGHt and fliGHt subjects who continued into the open-label long-term extension enliGHten trial (data cut: June 1st 2020). Subjects received either lonapegsomatropin (Group A; vial/syringe) or daily somatropin (Group B; pen device) in heiGHt, or lonapegsomatropin in fliGHt (Group C; vial/syringe). Upon entry into enliGHten, all subjects received lonapegsomatropin via vial/syringe, with subsequent switch to TransCon hGH Auto-Injector when available. Average IGF-1 was obtained on post-dose Day 5 (±1) in enliGHten. A by-visit ANCOVA model was used for numeric efficacy endpoints. Results: A total of 298 (98%) subjects continued into enliGHten. (A: n=103; B: n=55; C: n=140). The treatment difference in LS mean ∆ height SDS (A vs B) at the end of heiGHt (Week 52, 1.10 vs 0.96, P=0.015) was sustained through Week 104 (1.61 vs 1.49, P=0.158). For Group C, height SDS improved from −1.42 at fliGHt baseline to −0.69 at Week 78. AHV was within the expected range for 2nd year therapy. Among children who switched (B), an attenuation in the expected 2nd year decline of AHV suggested that lonapegsomatropin had an improved treatment effect relative to the previous daily somatropin. Mean (SD) average IGF-1 SDS remained stable and generally within the expected range for all groups (Week 104, A: 0.95 [1.22], B: 1.04 [1.25]; Week 78, C:1.81 [1.08]). An improvement in injection site tolerability was observed after switching to the TransCon hGH Auto-Injector; subjects and parents also indicated overall ease-of-use of the device (assessed by the Device Usability Questionnaire). With continued lonapegsomatropin treatment, the AE profile remained consistent with what was observed in the parent trials, with no new safety signals. Throughout enliGHten and the parent trials, non-neutralizing low-titer anti-hGH binding antibodies were detected post-dose in a total of 15 subjects (5.0%). Lab parameters were stable and generally remained within the normal range throughout the trials. As of the data cut, 2 subjects have achieved near adult height (AHV &lt;2 cm/year over the last 9 months or bone age &gt;14 [females] or &gt;16 [males]) and thus have completed the trial. Conclusions: Children treated with lonapegsomatropin showed continued improvement of height SDS through their 2nd year of therapy. Lonapegsomatropin continued to demonstrate a safety profile comparable to that of daily somatropin therapy.

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