Background: With growth hormone (GH) receptors present on virtually all cells, GH replacement therapy should aim for the same exposure and tissue distribution as endogenous GH and current daily GH therapies. The challenge to developing a long-acting GH (LAGH) is to establish the same safety, efficacy, and tolerability of daily GH, which includes maintaining GH and IGF-1 levels within the physiological range. To create a LAGH, two approaches have been used: 1) combine unmodified GH with a prolongation technology, or 2) modify GH providing a longer half-life. TransCon GH is a LAGH prodrug in development for pediatric growth hormone deficiency (GHD) with GH transiently bound to an inert carrier. It was designed to release unmodified GH over 7 days to achieve the same exposure, safety, efficacy, and tolerability as daily GH with more convenient once weekly dosing. This profile was successfully demonstrated in the Phase 2 trial in pediatric GHD. TransCon GH is also being developed with an autoinjector for ease of administration and improved adherence. Aims: We aim to present the topline 52-week pivotal Phase 3 results of TransCon GH in treatment of pediatric GHD. Methods: The phase 3 heiGHt trial was designed to compare safety, tolerability, and efficacy of weekly TransCon GH versus daily GH over 52 weeks in treatment-naive prepubertal children with GHD. Study endpoints include annualized height velocity (AHV), IGF-1 response, immunogenicity, and safety. Results: Top-line 52-week results of the heiGHt trial (N = 161) including AHV, Δ height SDS, IGF-1 levels, Δ bone age, and adverse events, will be available for presentation at PENS 2019. Conclusions: Only LAGHs based on unmodified GH have succeeded in providing both accelerated height velocity as well as reducing truncal adiposity in line with currently available daily GH therapies. Top-line data from the pivotal heiGHt trial of TransCon GH, a LAGH prodrug releasing unmodified GH, will be available in March 2019. Clinical Implications: A GH prodrug that provides sustained release of unmodified GH for the treatment of pediatric GHD would likely maintain the same tissue distribution as endogenous GH, with comparable efficacy, safety, tolerability, with the benefit of improved compliance due to weekly dosing via an autoinjector.
Background: Until recently, the only FDA approved treatments for adolescents with Type 2 diabetes (T2DM) were oral Metformin and subcutaneous insulin. The common gastrointestinal side effects to Metformin and the complicated regimen of insulin therapy have interfered with safe and healthy diabetes control in this population. Liraglutide was recently approved for treatment of children age 10 years and older with T2DM, representing a third treatment option. Purpose: The purpose of this poster is to describe a glucagon-like polypeptide-1 (GLP-1) agonist medication that will aid in beta cell preservation, diminish the need for insulin, promote weight loss, and may improve the lipid profile. Liraglutide can be used in combination with Metformin and/or insulin. Description of Topic: Liraglutide works by activating the GLP-1 receptor in the pancreatic beta cells, thereby causing increased insulin production in the presence of hyperglycemia. Dosing starts at 0.6 mg via subcutaneous daily injection. If tolerated, the dose is increased to 1.2 mg daily, and then to a maximum of 1.8 mg daily. This method of incremental increases is recommended to prevent gastrointestinal side effects. The most common side effects of liraglutide include nausea, vomiting, diarrhea, decreased appetite, constipation, and delayed gastric emptying. In addition, the risk of hypoglycemia in adolescents is increased with liraglutide. Clinical Implications: Liraglutide has several clinical benefits. It aids in the preservation of beta cells which can decrease or phase out the need for insulin. Since insulin excess promotes higher fat stores in the body, eliminating insulin should result in weight loss and increased insulin sensitivity. The goal of Liraglutide therapy is to lower the hemoglobin A1C, decreasing the risk of complications related to diabetes.
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