scholarly journals SAT-LB12 Once-Weekly Somapacitan vs Daily Growth Hormone in Growth Hormone Deficiency: 2-Year Safety Results From Real 3, a Randomized Phase 2 Trial

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lars S Savendahl ◽  
Michael Højby Rasmussen
Keyword(s):  
Growth Hormone ◽  
Injection Site ◽  
Gh Deficiency ◽  
Controlled Trial ◽  
Hormone Deficiency ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Gh Treatment ◽  
Treatment Groups ◽  
Injection Site Reactions

Abstract Growth hormone (GH) replacement therapy currently requires daily injections. Somapacitan is a long-acting GH-derivative being developed for once-weekly (OW) use in children and adults with GH deficiency (GHD). A phase 2, multinational, randomized, open-label, controlled trial (ClinicalTrials.gov: NCT02616562) investigated the efficacy and safety of OW somapacitan compared with daily GH (Norditropin® FlexPro®). GH-treatment-naïve prepubertal children with GH deficiency received 0.04 (n=16), 0.08 (n=15) or 0.16 mg/kg/wk (n=14) subcutaneous (sc) OW somapacitan, or sc GH 0.034 mg/kg/day (0.24 mg/kg/wk; n=14) for 52 wks, followed by a 104-wk safety extension with all patients on somapacitan receiving 0.16 mg/kg/wk while GH dose was unaltered. Safety endpoints included frequency of adverse events (AEs), including injection-site reactions, and occurrence of anti-somapacitan/anti-human growth hormone (hGH) antibodies. The 52-wk efficacy and safety results have been reported. We report here safety results at 104 wks’ total treatment. Number of AEs (% of patients) was as follows: OW somapacitan 0.04/0.16 mg/kg/wk, 51 (75%); 0.08/0.16 mg/kg/wk, 89 (80%); 0.16/0.16 mg/kg/wk, 89 (100%); and for daily GH, 82 (100%). Nasopharyngitis, influenza, allergic rhinitis and gastroenteritis were the most common AEs across all treatment groups. Pyrexia was more common in the OW somapacitan 0.04/0.16 mg/kg/wk (43.8%) and 0.08/0.16 mg/kg/wk (26.7%) groups vs the higher-dose OW somapacitan and daily GH groups (7.1% each). Most AEs were mild to moderate and unlikely related to treatment. Ten serious AEs were reported in five (8.5%) children and unlikely related to treatment, except two AEs of moderate severity during the first 26 wks: generalized edema and vomiting in one child on 0.16 mg/kg/wk OW somapacitan, rated as probably related to treatment although she was also given intravenous antibiotics for suspected infection. Injection-site reactions were reported in the 0.04/0.16 mg/kg/wk (n=2) and 0.16/0.16 mg/kg/wk (n=1) OW somapacitan groups and in the daily GH group (n=1). Four children (0.04/0.16 mg/kg/wk) and one child (0.16/0.16 mg/kg/wk) had transient anti-somapacitan antibodies; one child (0.16/0.16 mg/kg/wk) had low-titer anti-somapacitan antibodies at two consecutive visits; in one child (daily GH group) with persistent low-titer anti-hGH antibodies, treatment was discontinued at wk 52. All antibodies were non-neutralizing. In conclusion, OW somapacitan was well tolerated at all doses, with no new safety or tolerability issues identified after up to 104 wks of treatment. The frequency, severity and type of AEs were similar in the OW somapacitan and daily GH treatment groups except for pyrexia, which was unlikely related to treatment and more frequently reported in the lowest dose somapacitan group.

scholarly journals Once-Weekly Somapacitan Versus Daily Growth Hormone in Growth Hormone Deficiency: 2-Year Efficacy Results From REAL 3, a Randomized Phase 2 Trial

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A680-A680
Author(s):  
Lars S Sävendahl ◽  
Tadej Battelino ◽  
Michael Højby Rasmussen ◽  
Reiko Horikawa ◽  
Paul Saenger
Keyword(s):  
Growth Hormone ◽  
Standard Deviation ◽  
Height Velocity ◽  
First Year ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Gh Treatment ◽  
Treatment Groups ◽  
Igf I ◽  
Second Year

Abstract Current treatment for growth hormone (GH) deficiency (GHD) requires daily injections, which can be burdensome for the patients/caregivers. Once-weekly somapacitan is a long-acting GH derivative currently in phase 3 for use in children with GHD and phase 2 for short children born small for gestational age. A phase 2, multinational, randomized, open-label, controlled trial (NCT02616562) investigated the efficacy and safety of somapacitan in children compared with daily GH (Norditropin®). GH-treatment-naïve prepubertal children with GHD received 0.04 (n=16), 0.08 (n=15) or 0.16 mg/kg/week (n=14) subcutaneous (s.c.) somapacitan, or s.c. daily GH 0.034 mg/kg/day (0.24 mg/kg/week; n=14) for 52 weeks, followed by a 104-week safety extension. In the extension phase, all patients on somapacitan received 0.16 mg/kg/week; daily GH dose remained unaltered. The 52-week efficacy and safety results have been reported previously. We report here the efficacy results after 104 weeks of GH treatment. At week 104, mean (standard deviation [SD]) height velocity (HV) in the first year of the safety extension was: 10.6 (1.4), 10.0 (1.6) and 9.2 (1.7) cm/year for 0.04/0.16 mg/kg/week (n=13), 0.08/0.16 mg/kg/week (n=15) and 0.16/0.16 mg/kg/week (n=14) somapacitan, respectively, versus 9.0 (2.3) cm/year for daily GH (n=11). Mean (SD) change from baseline in HV standard deviation score (SDS) was 8.04 (2.52), 6.21 (2.90) and 6.40 (3.04) for somapacitan, respectively, versus 6.58 (3.15) for daily GH. Compared with week 52, mean HV and HV SDS at week 104 were increased in children in the somapacitan 0.04/0.16 mg/kg/week and 0.08/0.16 mg/kg/week treatment groups. Height SDS values improved during the second year of treatment with somapacitan and daily GH, with the greatest change from baseline in the somapacitan 0.16/0.16 mg/kg/week treatment group. The mean (SD) change in height SDS from baseline to week 104 was 1.73 (0.76), 1.87 (0.81) and 2.18 (1.18) for somapacitan, respectively, versus 1.72 (0.65) for daily GH. The observed mean (SD) change in insulin-like growth factor-I (IGF-I) SDS from baseline was similar between the somapacitan 0.08/0.16 and 0.16/0.16 mg/kg/week treatment groups (3.15 [1.17] and 3.21 [1.12], respectively), and slightly higher compared with IGF-I SDS in the 0.04/0.16 mg/kg/week group (2.99 [1.05]) and the daily GH group (3.06 [1.26]). Mean IGF-I SDS values remained below the upper limit (+2) of the normal range for all treatment groups throughout the 104-week trial duration. Somapacitan was well tolerated at all doses investigated, with no new safety or local tolerability issues identified during the 104 weeks of treatment. In conclusion, at week 104, height-based outcomes were similar between somapacitan 0.16/0.16 mg/kg/week and daily GH, with comparable mean change in IGF-I SDS. Furthermore, the key improvements observed in the first year were maintained in the second year of the study.

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).

Advances in the Understanding of Adult Growth Hormone Deficiency Syndrome – Diagnosis, Epidemiology and Management

2010 ◽  
Vol 6 (2) ◽  
pp. 45
Author(s):  
Torben Laursen ◽  
Keyword(s):  
Growth Hormone ◽  
Cardiovascular Diseases ◽  
Dynamic Testing ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Deficiency Syndrome ◽  
Hormone Deficiency ◽  
Gh Treatment ◽  
Adult Growth ◽  
Increased Risk

In patients with hypopituitarism, growth hormone (GH) deficiency is almost always present. Lack of other pituitary hormones may require prompt replacement, but lack of GH is also associated with several abnormalities, which can be improved by GH treatment. The aberrations include low bone mass and increased risk of fractures, abnormal body composition, e.g. increased fat mass and reduced lean body mass resulting in reduced muscle mass and strength. Decreased exercise capacity may be influenced by impaired cardiac performance and heat intolerance. Increased abdominal fat results in metabolic disturbancies, such as reduced insulin sensitivity and hyperlipidaemia, increasing the risk of cardiovascular diseases. Patients with hypopituitarism replaced with relevant hormones except GH have increased mortality due to cardiovascular diseases and increased morbidity. Thus, it is important to diagnose GH deficiency, which requires precise diagnostic criteria and methods. Dynamic testing of GH secretion with an insulin tolerance test or arginine plus GH-releasing hormone can be used.

scholarly journals Impact of the underlying etiology of growth hormone deficiency on serum IGF-I SDS levels during GH treatment in children

2017 ◽  
Vol 177 (3) ◽  
pp. 267-276 ◽  
Author(s):  
Juliane Léger ◽  
Damir Mohamed ◽  
Sophie Dos Santos ◽  
Myriam Ben Azoun ◽  
Delphine Zénaty ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Care Center ◽  
Treatment Compliance ◽  
Hormone Deficiency ◽  
Pediatric Care ◽  
Pituitary Hormone ◽  
Gh Treatment ◽  
Pubertal Stage ◽  
Igf I

ContextRegular monitoring of serum IGF-I levels during growth hormone (GH) therapy has been recommended, for assessing treatment compliance and safety.ObjectiveTo investigate serum IGF-I SDS levels during GH treatment in children with GH deficiency, and to identify potential determinants of these levels.Design, patients and methodsThis observational cohort study included all patients (n = 308) with childhood-onset non-acquired or acquired GH deficiency (GHD) included in the database of a single academic pediatric care center over a period of 10 years for whom at least one serum IGF-I SDS determination during GH treatment was available. These determinations had to have been carried out centrally, with the same immunoradiometric assay. Serum IGF-I SDS levels were determined as a function of sex, age and pubertal stage, according to our published normative data.ResultsOver a median of 4.0 (2–5.8) years of GH treatment per patient, 995 serum IGF-I SDS determinations were recorded. In addition to BMI SDS, height SDS and GH dose (P < 0.01), etiological group (P < 0.01) had a significant effect on serum IGF-I SDS levels, with patients suffering from acquired GHD having higher serum IGF-I SDS levels than those with non-acquired GHD, whereas sex, age, pubertal stage, treatment duration, hormonal status (isolated GHD (IGHD) vs multiple pituitary hormone deficiency (MPHD)) and initial severity of GHD, had no effect.ConclusionsThese original findings have important clinical implications for long-term management and highlight the need for careful and appropriate monitoring of serum IGF-I SDS and GH dose, particularly in patients with acquired GHD, to prevent the unnecessary impact of potential comorbid conditions.

scholarly journals Malignancy risk in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope®): data from the PATRO Adults study

2020 ◽  
Vol 11 ◽  
pp. 204201882094337
Author(s):  
Paolo Beck-Peccoz ◽  
Charlotte Höybye ◽  
Robert D Murray ◽  
Suat Simsek ◽  
Markus Zabransky ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Real Life ◽  
Hormone Deficiency ◽  
System Organ Class ◽  
Pituitary Hormone ◽  
Gh Treatment ◽  
Post Marketing Surveillance ◽  
Increased Risk ◽  
Long Term Treatment

Background: To assess the safety (particularly the occurrence of malignancies) of growth hormone (GH) replacement (Omnitrope®) in adults with GH deficiency, using data from the ongoing PATRO Adults post-marketing surveillance study. Methods: PATRO Adults is being conducted in hospitals and specialized endocrinology clinics across Europe. All enrolled patients who receive ⩾1 dose of Omnitrope® are included in the safety population. Malignancies are listed as adverse events under the MedDRA System Organ Class ‘neoplasms, benign, malignant and unspecified (including cysts and polyps)’. Results: As of July 2018, 1293 patients had been enrolled in the study and 983 (76.0%) remained active in the study. Approximately half [ n = 637 (49.3%)] of the patients were GH treatment-naïve on study entry. The majority of enrolled patients had multiple pituitary hormone deficiency ( n = 1128, 87.2%). A total of 41 on-study malignancies were reported in 33 patients (2.6%; incidence rate 7.94 per 1000 patient-years). The most common cancers were basal cell carcinoma ( n = 13), prostate ( n = 6), breast, kidney and malignant melanoma (each n = 3). Treatment with Omnitrope® was discontinued following diagnosis of malignancy in 16 patients. The tumors occurred after a mean of 79.4 months of recombinant hormone GH (rhGH) treatment overall. Conclusion: Based on this snapshot of data from PATRO Adults, Omnitrope® treatment is tolerated in adult patients with GH deficiency in a real-life clinical practice setting. Our results do not generally support a carcinogenic effect of rhGH in adults with GH deficiency, although an increased risk of second new malignancies in patients with previous cancer cannot be excluded based on the current dataset.

Short stature in a boy with atypical progeria syndrome due to LMNA c.433G>A [p.(Glu145Lys)]: apparent growth hormone deficiency but poor response to growth hormone therapy

2019 ◽  
Vol 32 (7) ◽  
pp. 775-779
Author(s):  
Ledjona Toni ◽  
Petra Dušátková ◽  
Dana Novotná ◽  
Daniela Zemková ◽  
Štěpánka Průhová ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Empty Sella ◽  
Premature Aging ◽  
Hormone Deficiency ◽  
Gh Treatment ◽  
Term Outcome ◽  
Poor Growth ◽  
Long Term Outcome ◽  
Progeria Syndrome

Abstract Background Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by pathogenic variants in the LMNA gene, which leads to premature aging. The median life expectancy is shortened to 13 years due to cardiovascular complications. Case report We present a boy born with a pathogenic LMNA variant c.433G > A, which causes atypical progeria syndrome (APS) and was previously described in one single patient. When investigated for poor growth prior to the diagnosis of APS, his laboratory tests revealed growth hormone (GH) deficiency and magnetic resonance imaging (MRI) of the midbrain showed partial empty sella. GH treatment had only a limited and transient effect. His first ischemic complication manifested at age 4.2 years; at the age of 7 years, he had a fatal haemorrhagic stroke. Conclusion To the best of our knowledge, this is the first patient with APS showing partial empty sella and GH deficiency that might have contributed to his poor growth. GH failed to improve long-term outcome.

Lower ability to oxidize lipids in adult patients with growth hormone (GH) deficiency: reversal under GH treatment

2006 ◽  
Vol 65 (4) ◽  
pp. 423-428 ◽  
Author(s):  
F. Brandou ◽  
I. Aloulou ◽  
A. Razimbaud ◽  
C. Fédou ◽  
J. Mercier ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Adult Patients ◽  
Gh Treatment ◽  
Lower Ability
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