24-Month Use of Once-Weekly GH, LB03002, in Prepubertal Children With GH Deficiency

Khadilkar, Vaman; Radjuk, K.A.; Большова, Е В; Khadgawat, Rajesh; Kholy, Mohamed El; Desai, Meena; Peterkova, Valentina; Mericq, Verónica; Kratzsch, Jürgen; Siepl, E. Christine; Martin, Dieter; Lopez, Prema; Ji, Hyi-Jeong; Bae, Yoon Ju; Lee, Jin Hwa; Saenger, Paul

doi:10.1210/jc.2013-2502

Cited by 47 publications

(46 citation statements)

References 20 publications

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“…It was withdrawn in 2004 due to the significant resources required by the companies to continue the manufacturing and commercialising of the product. LB03002 is a sustained release preparation of GH incorporated into sodium hyaluronate microparticles that has demonstrated similar efficacy to daily GH in prepubertal GH naïve children with GHD (Khadilkar et al 2014). There are many other long-acting GH preparations under development utilising hydrogels, implants and modifications of GH by pegylation, conjugation with albumin, conjugation with specific amino acid sequences (XTEN) and fusion to Fc domains of human immunoglobulin (Cai et al 2014).…”

Section: Gh Deficiencymentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-GH axis: the past 60 years

Murray¹,

Higham²,

Clayton³

2015

Journal of Endocrinology

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At the time of the publication of Geoffrey Harris's monograph on 'Neural control of the pituitary gland' 60 years ago, the pituitary was recognised to produce a growth factor, and extracts administered to children with hypopituitarism could accelerate growth. Since then our understanding of the neuroendocrinology of the GH axis has included identification of the key central components of the GH axis: GH-releasing hormone and somatostatin (SST) in the 1970s and 1980s and ghrelin in the 1990s. Characterisation of the physiological control of the axis was significantly advanced by frequent blood sampling studies in the 1980s and 1990s; the pulsatile pattern of GH secretion and the factors that influenced the frequency and amplitude of the pulses have been defined. Over the same time, spontaneously occurring and targeted mutations in the GH axis in rodents combined with the recognition of genetic causes of familial hypopituitarism demonstrated the key factors controlling pituitary development. As the understanding of the control of GH secretion advanced, developments of treatments for GH axis disorders have evolved. Administration of pituitary-derived human GH was followed by the introduction of recombinant human GH in the 1980s, and, more recently, by long-acting GH preparations. For GH excess disorders, dopamine agonists were used first followed by SST analogues, and in 2005 the GH receptor blocker pegvisomant was introduced. This review will cover the evolution of these discoveries and build a picture of our current understanding of the hypothalamo-GH axis.

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Section: Gh Deficiencymentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-GH axis: the past 60 years

Murray¹,

Higham²,

Clayton³

2015

Journal of Endocrinology

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“…High-dose rhGH therapy (0.7 mg/kg/week, daily) had previously been demonstrated to be effective and safe in GH-deficient adolescents who were most growth-retarded at the onset of puberty [25]. Finally, the PK/PD profiles of LB03002 administered at either 0.5 or 0.7 mg/kg/week were shown to be suitable for a long-term treatment of children with GHD [16, 26]. Although the PK/PD profiles of LB03002 in children with ISS were out of the scope of the present study, sparse data on the dynamics of hGH, IGF-I, and IGFBP-3 levels imply that they may be similar to those documented previously in GHD patients.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the safety profiles of LB03002 at both doses administered to children with ISS for 26 weeks were assessed to be acceptable and comparable with that of the control. Meanwhile, favorable long-term (2–3 years) safety data of LB03002 can be referenced both from the phase II/III [26] and phase III [16] studies conducted in GHD children.…”

Section: Discussionmentioning

confidence: 99%

“…is a once-weekly sustained-release formulation of rhGH manufactured using genetically modified Saccharomyces cerevisiae and contained in sodium hyaluronate microparticles suspended in medium-chain triglycerides prior to injection [13]. The efficacy and safety of LB03002 were confirmed in children and adults with GHD [14-16]. Up to date, however, there is no evidence confirming the efficacy of the once-weekly formulation in ISS patients.…”

Section: Introductionmentioning

confidence: 99%

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Once-Weekly Administration of Sustained-Release Growth Hormone in Korean Prepubertal Children with Idiopathic Short Stature: A Randomized, Controlled Phase II Study

Hwang

Lee

et al. 2018

Horm Res Paediatr

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Background/Aims: To determine the optimal dose of LB03002, a sustained-release, once-weekly formulation of recombinant human growth hormone (rhGH), and to compare its efficacy and safety with daily rhGH in children with idiopathic short stature (ISS). Methods: This multicenter, randomized, open-label, phase II study included GH-naïve, prepubertal children with ISS, randomized to receive daily rhGH 0.37 mg/kg/week (control, n = 16), LB03002 0.5 mg/kg/week (n = 14), or LB03002 0.7 mg/kg/week (n = 16). The primary endpoint was height velocity (HV) change at week 26. Results: At week 26, the least square (LS) means for HV change (cm/year) with control, LB03002 0.5 mg/kg/week, and LB03002 0.7 mg/kg/week were 5.08, 3.65, and 4.38, and the LS means for the change in height standard deviation score were 0.65, 0.49, and 0.58, respectively. The lower bound of the 90% confidence interval for the difference between LB03002 0.7 mg/kg/week and the control in the LS mean for HV change (–1.72) satisfied the noninferiority margin (–1.75). Adverse events were generally mild and short-lived. Conclusion: A once-weekly regimen of LB03002 0.7 mg/kg demonstrated noninferiority to the daily regimen of rhGH 0.37 mg/kg/week in terms of HV increments. LB03002 was well tolerated and its safety profile was comparable with that of daily rhGH.

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“…To date, a number of LAGH formulations have been studied [2], and their efficacy in phase 2 studies is quite good [3]. The only successful phase 3 study that led to the approval of LAGH for pediatric and adult growth hormone deficiency (GHD) in Europe was done with the same formulation used by Hwang and coworkers [4]. …”

mentioning

confidence: 99%