hrp0089fc2.1 | Bone, Growth Plate & Mineral Metabolism 1 | ESPE2018

Burosumab, a Fully Human anti-FGF23 Monoclonal Antibody, for X-linked Hypophosphatemia (XLH): Sustained Improvement in two Phase 2 Trials in Affected Children 1–12 years old

Linglart Agnes , van't Hoff William , Whyte Michael P. , Imel Erik , Portale Anthony A. , Boot Annemieke , Hogler Wolfgang , Padidela Raja , Mao Meng , Skrinar Alison , Martin Javier San , Carpenter Thomas O.

In XLH, excess fibroblast growth factor 23 (FGF23) causes hypophosphatemia and consequent rickets, skeletal deformities, and growth impairment. The efficacy and safety of burosumab, a fully human monoclonal antibody against FGF23, was evaluated in two Phase 2 trials in children with XLH. In CL201, 52 children with XLH (5–12 years old, Tanner ≤2) were randomized 1:1 to receive subcutaneous burosumab every 2 (Q2W) or 4 (Q4W) weeks, with doses titrated up to 2 mg/kg to...

hrp0092fc2.1 | Bone, Growth Plate and Mineral Metabolism Session 1 | ESPE2019

Continued Improvement in Clinical Outcomes with Burosumab, a Fully Human Anti-FGF23 Monoclonal Antibody: Results from a 3-Year, Phase 2, Clinical Trial in Children with X-Linked Hypophosphatemia (XLH)

Linglart Agnès , Carpenter Thomas O. , Högler Wolfgang , Imel Erik A. , Portale Anthony A. , Boot Annemieke , Padidela Raja , Van't Hoff William , Mao Meng , Skrinar Alison , Scott Roberts Mary , San Martin Javier , Whyte Michael P.

In children with XLH, excess FGF23 causes hypophosphatemia with consequent rickets, skeletal deformities, and impaired growth and mobility. We previously reported that burosumab improved phosphate homeostasis and rickets in children with XLH. Here, we report final data from this Phase 2 Study CL201 (NCT02163577).Fifty-two children with XLH (5-12 years old, Tanner ≤ 2) were randomized 1:1 to receive subcutaneous burosumab every 2 (Q2W) or 4 (Q4W) we...

hrp0092fc2.2 | Bone, Growth Plate and Mineral Metabolism Session 1 | ESPE2019

Benefits of Long-Term Burosumab Persist in 11 Girls with X-Linked Hypophosphatemia (XLH) Who Transitioned into Adolescence During the Phase 2 CL201 Trial

Boot Annemieke , Carpenter Thomas O. , Högler Wolfgang , Imel Erik A. , Portale Anthony A. , Linglart Agnès , Padidela Raja , Van't Hoff William , Mao Meng , Skrinar Alison , Scott Roberts Mary , San Martin Javier , Whyte Michael P.

In children with XLH, excess FGF23 causes hypophosphatemia with consequent rickets, skeletal deformities, and impaired growth and mobility. We reported that burosumab improved phosphate homeostasis and rickets in children with XLH. Here, we present data on 11/52 subjects (all girls) who developed fused growth plates during the phase 2 study CL201 (NCT02163577).In CL201, 52 subjects (Baseline: 5-12 years-old, Tanner ≤ 2) were randomized 1:1 to recei...

hrp0086fc2.6 | Bone & Mineral Metabolism | ESPE2016

Effect of KRN23, a Fully Human Anti-FGF23 Monoclonal Antibody, on Rickets in Children with X-linked Hypophosphatemia (XLH): 40-week Interim Results from a Randomized, Open-label Phase 2 Study

Linglart Agnes , Carpenter Thomas , Imel Erik , Boot Annemieke , Hogler Wolfgang , Padidela Raja , van't Hoff William , Whyte Michael , Chen Chao-Yin , Skrinar Alison , Agarwal Sunil , Martin Javier San , Portale Anthony

Background: In XLH, high circulating FGF23 causes hypophosphatemia, rickets, and short stature.Objective and hypotheses: To evaluate KRN23 effects on serum phosphate (Pi) level and rickets severity in XLH children in a Phase 2 study.Method: 52 XLH children (ages 5–12 years, ≤Tanner 2) received KRN23 subcutaneously biweekly (Q2W) or monthly (Q4W). Serum Pi was measured at 2-week intervals. KRN23 dose was titrated (maximum...

hrp0082s2.3 | Endocrine Cancer Syndromes: An Update | ESPE2014

DICER1 Syndrome: A Review of the Syndrome with a Focus on Endocrine Aspects

Foulkes William

Background: DICER1, a ribonuclease, cleaves non-coding small RNA precursors to generate mature microRNAs (miRNAs), of ~21 nucleotides in length. MiRNAs alter gene expression post-transcriptionally by directly binding to mRNA transcripts and subsequently down-regulating gene expression. It is estimated that expression of ~30–70% of all mammalian protein-coding genes are regulated in this manner.Method: Sequencing of DICER1 in various tumors, accompan...

hrp0082s5.2 | Novel Insights into Hypoadrenalism | ESPE2014

Adrenarche: Coming of Age in the Era of Genomics and Metabolomics

Rainey William

The human adrenal cortex produces a wide range of steroids that includes aldosterone, cortisol and a variety of 19 carbon (C19) steroids; the most studied being DHEA. In humans, adrenarche is the endocrine developmental process manifested by an increased adrenal output of DHEA. This phenomenon corresponds with the expansion of the zona reticularis of the adrenal gland. However, the physiological mechanisms that trigger adrenarche remain elusive. Our research focuses...

hrp0094pl2 | Coming soon: new drugs for treatment of youth with type 2 diabetes | ESPE2021

New Drugs for Youth with Type 2 Diabetes

Tamborlane William

Metformin was the first and only drug approved in 1999 for use in youth with type 2 diabetes (T2D) based on a small, randomized clinical trial. Insulin was also approved but this was based only on the effective use of insulin in children with T1D. For more than 20 years, no new drugs had been approved for use in pediatric T2D based on a randomized study. A major reason why many of the new drugs have not been approved in pediatrics is that adolescents with T2D are difficult to ...

hrp0086p2-p720 | Endocrinology and Multisystemic Diseases P2 | ESPE2016

Familial Williams Syndrome

Isguven Sukriye Pinar , Aydin Dilek Bingol , Karkucak Mutlu

Background: Williams Syndrome (WS) is a multisystemic genetic syndrome, which includes characteristic appearance of “elfian face”, growth retardation, mild mental retardation, hypersociality, infantile hypercalcemia, and other endocrine, cardiovascular, and urinary abnormalities. WS is caused by the microdeletion of chromosome 7q11.23; it is usually sporadic but rare autosomal dominant familial cases have been reported in the literature. We present a boy and his moth...

hrp0084p3-673 | Bone | ESPE2015

Successful Treatment of Severe Hypercalcemia in an Infant with Williams Syndrome Using a Single Infusion of Pamidronate Followed by Low Calcium Diet

Odeh Rasha , Albaramki Jumana , Alassaf Abeer

Background: 15% of patients with Williams syndrome develop hypercalcemia that is described as mild and transient. There are, however, reported cases with severe hypercalcemia that did not respond to traditional therapy. Pamidronate was used in the treatment of this condition, and was successful in the few reported cases in the literature.Case presentation: We report a 9 month old female who presented with failure to thrive, polyuria and polydipsia. She h...

hrp0086p2-p146 | Bone & Mineral Metabolism P2 | ESPE2016

Bone Mineral Status and Metabolism in Patients with Williams-Beuren Syndrome

Stagi Stefano , Scalini Perla , Chiarelli Francesco , Verrotti Alberto , Giglio Sabrina , Ricci Franco , Lapi Elisabetta , Romano Silvia , Martino Maurizio de

Background: Despite the multiple endocrine, cardiovascular, and gastroenterologic problems of patients with Williams-Beuren Syndrome (WBS), Studies considering metabolism and bone quality in WBS are almost entirely absent from the literature.Objective and hypotheses: We evaluate bone mineral status and metabolism in a cohort of patients with WBS.Method: Thirty-one children (15 females, 16 male...