OR7-6: Safety and efficacy of ARX201: six month dose-ranging study of a novel long-acting pegylated growth hormone in young adults with growth hormone deficiency

Rácz, Károly; Coculescu, M; Olyinik, V.; Popa, Mónica; Popović, Vera; Radiuk, K.; Сенаторова, Анна Сергеевна; Vlasenkо, М.V.; Norman, Trevor R.; Juhasz, Mihaly; Hoffman, Andrew R.; Axelrod, Douglas W.

doi:10.1016/s1096-6374(14)50052-4

Cited by 3 publications

(2 citation statements)

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“…In a 6 month phase 2 study of 43 young adults with childhood onset GHD ARX201 was shown to be well-tolerated and improved body composition, lipid profile and quality of life [38]. A dose dependent increase in IGF-I was observed [39]. However, PEG-containing vacuoles were discovered in the epithelial cells of the choroid plexus in monkeys treated with ARX201 and development has been discontinued.…”

Section: Arx201mentioning

confidence: 99%

Status of long-acting-growth hormone preparations — 2015

Höybye

Cohen

Hoffman

et al. 2015

Growth Hormone & IGF Research

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Section: Arx201mentioning

confidence: 99%

Status of long-acting-growth hormone preparations — 2015

Höybye

Cohen

Hoffman

et al. 2015

Growth Hormone & IGF Research

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“…While PEG remains the best characterized inert polymer for modifying biopharmaceuticals and has demonstrated safety and tolerability in chronic settings, repeat parenteral administration of PEGylated proteins to animals has in some cases been associated with vacuolation – the formation of enclosed intracellular compartments for clearance of debris – in macrophages and/or histiocytes of various organs, including renal tubular cells ( 33 ). Formation of vacuoles in the choroid plexus of cynomolgus monkeys have been reported for a permanently PEGylated GH analogue, ARX201, which was being developed by Ambrx ( 34 ). Vacuolation, which occurs mainly in phagocytes, has not been linked to organ dysfunction in toxicology studies, and the body of evidence for approved PEGylated biopharmaceuticals has not identified any clinical consequences for compounds where vacuolation was observed in toxicology studies ( 35 ).…”

Section: True Replacement Therapy With Convenient Dosingmentioning

confidence: 99%

The rationale and design of TransCon Growth Hormone for the treatment of growth hormone deficiency

Sprogoe

Mortensen²,

Karpf³

et al. 2017

Endocrine Connections

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The fundamental challenge of developing a long-acting growth hormone (LAGH) is to create a more convenient growth hormone (GH) dosing profile while retaining the excellent safety, efficacy and tolerability of daily GH. With GH receptors on virtually all cells, replacement therapy should achieve the same tissue distribution and effects of daily (and endogenous) GH while maintaining levels of GH and resulting IGF-1 within the physiologic range. To date, only two LAGHs have gained the approval of either the Food and Drug Administration (FDA) or the European Medicines Agency (EMA); both released unmodified GH, thus presumably replicating distribution and pharmacological actions of daily GH. Other technologies have been applied to create LAGHs, including modifying GH (for example, protein enlargement or albumin binding) such that the resulting analogues possess a longer half-life. Based on these approaches, nearly 20 LAGHs have reached various stages of clinical development. Although most have failed, lessons learned have guided the development of a novel LAGH. TransCon GH is a LAGH prodrug in which GH is transiently bound to an inert methoxy polyethylene glycol (mPEG) carrier. It was designed to achieve the same safety, efficacy and tolerability as daily GH but with more convenient weekly dosing. In phase 2 trials of children and adults with growth hormone deficiency (GHD), similar safety, efficacy and tolerability to daily GH was shown as well as GH and IGF-1 levels within the physiologic range. These promising results support further development of TransCon GH.

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Formulations and Technologies in Growth Hormone Delivery

Mohammed

Obaidat

Assaf

et al. 2017

Int J Pharm Pharm Sci

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Growth hormone (GH) treatment has many indications including the treatment of growth hormone deficiency (GHD), Prader-Willi syndrome, chronic renal insufficiency, Turner syndrome, AIDS-related wasting, idiopathic short stature in children, and accumulation of fat which related in adults with lipodystrophy. Conventional therapy was achieved using daily intramuscular (IM) and subcutaneous (SC) injections. However, patient's noncompliance was very high. To solve this; several studies have been attempted to prepare long-acting formulations and to make prolonged halflife derivatives of GH. New delivery systems were also used such as needle-free and auto-injector devices to enhance the conveniences and adjustability. Furthermore, alternative routes of administration, such as intranasal, pulmonary, transdermal and oral are other strategies used to deliver the GH in a noninvasive way. In this review, we present a summary of various sustained-release formulations and technologies via injection. Noninvasive routes of GH delivery will be also reviewed with the principles of key points, selected additives, and limitations.

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OR7-6: Safety and efficacy of ARX201: six month dose-ranging study of a novel long-acting pegylated growth hormone in young adults with growth hormone deficiency

Cited by 3 publications

References 0 publications

Status of long-acting-growth hormone preparations — 2015

Status of long-acting-growth hormone preparations — 2015

The rationale and design of TransCon Growth Hormone for the treatment of growth hormone deficiency

Formulations and Technologies in Growth Hormone Delivery

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