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...

hrp0082fc2.5 | Bone & Mineral | ESPE2014

Pharmacokinetics and Pharmacodynamics of a Human Monoclonal Anti-Fibroblast Growth Factor 23 Antibody (KRN23) Following 4 Month Intra-Dose Escalation in Adults with X-Linked Hypophosphatemia

Zhang Xiaoping , Imel Erik , Ruppe Mary , Weber Thomas , Klausner Mark , Ito Takahiro , Vergeire Maria , Humphrey Jeffrey , Glorieux Francis , Portale Anthony , Insogna Karl , Peacock Munro , Carpenter Thomas

Background: In X-linked hypophosphatemia (XLH), abnormally elevated serum fibroblast growth factor 23 (FGF23) results in low renal maximum threshold for phosphate reabsorption (TmP/GFR), low serum phosphorus (Pi), inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2D) and development of rachitic deformities.Methods: Up to four s.c. KRN23 doses were given every 28 days to 28 adults with XLH according to a dose-escalation algorithm (0.05&#1...

hrp0082fc2.6 | Bone & Mineral | ESPE2014

Efficacy and Safety Following 4 Monthly s.c. Doses of a Human Anti-Fibroblast Growth Factor 23 Antibody (KRN23) in Adults with X-linked Hypophosphatemia

Peacock Munro , Imel Erik , Zhang Xiaoping , Ruppe Mary , Weber Thomas , Klausner Mark , Ito Takahiro , Vergeire Maria , Humphrey Jeffrey , Glorieux Francis , Portale Anthony , Insogna Karl , Carpenter Thomas

Background: In X-linked Hypophosphatemia (XLH), abnormally elevated serum Fibroblast Growth Factor 23 (FGF23) results in low renal maximum threshold for phosphate reabsorption (TmP/GFR), low serum phosphorus (Pi), inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2D) and development of rachitic deformities.Methods: Up to four SC KRN23 doses were given every 28 days to 28 adults with XLH (26 completed) according to a dose-escalation algorithm (0.05&...

hrp0082p1-d2-35 | Bone | ESPE2014

Assessment of Quality of Life Data After 4 Monthly S.C. Doses of a Human Monoclonal Anti-Fibroblast Growth Factor 23 Antibody (KRN23) in Adults with X-linked Hypophosphatemia

Ruppe Mary , Zhang Xiaoping , Imel Erik , Weber Thomas , Klausner Mark , Ito Takahiro , Vergeire Maria , Humphrey Jeffrey , Glorieux Francis , Portale Anthony , Insogna Karl , Peacock Munro , Carpenter Thomas

Objectives: In X-linked hypophosphatemia (XLH), abnormally elevated serum Fibroblast growth Factor 23 (FGF23) results in low renal maximum threshold for phosphate reabsorption, low serum phosphorus, inappropriately normal 1,25-dihydroxyvitamin D, and development of rachitic deformities. The effect of KRN23 on health-related quality of life (HRQL) was assessed.Methods: Open-label KRN23 was given s.c. every 28 days up to four doses to 28 adults with XLH (2...

hrp0092rfc2.1 | Bone, Growth Plate and Mineral Metabolism Session 1 | ESPE2019

Burosumab Resulted in Better Clinical Outcomes Than Continuation with Conventional Therapy in Both Younger (1-4 Years-Old) and Older (5-12 Years-Old) Children with X-Linked Hypophosphatemia

Högler Wolfgang , Imel Erik A. , Whyte Michael P. , Munns Craig , Portale Anthony A. , Ward Leanne , Nilsson Ola , Simmons Jill H. , Padidela Raja , Namba Noriyuki , Cheong Hae Il , Mao Meng , Skrinar Alison , San Martin Javier , Glorieux Francis

In children with X-linked hypophosphatemia (XLH), excess circulating fibroblast growth factor 23 (FGF23) causes hypophosphatemia with consequent rickets, skeletal deformities, and impairments in growth and mobility. Compared to continuation with conventional therapy (oral phosphate and active vitamin D [Pi/D]), switching to treatment with burosumab, a fully human monoclonal antibody against FGF23, showed significantly greater improvement in phosphate homeostasis, rickets sever...

hrp0089fc10.1 | Late Breaking | ESPE2018

Burosumab Improved Rickets, Phosphate Metabolism, and Clinical Outcomes Compared to Conventional Therapy in Children with X-Linked Hypophosphatemia (XLH) – A Randomized Controlled Phase 3 Study

Nilsson Ola , Whyte Michael P. , Imel Erik A. , Munns Craig , Portale Anthony A. , Ward Leanne , Simmons Jill H. , Padidela Raja , Namba Noriyuki , Cheong Hae Il , Mao Meng , Skrinar Alison , Chen Chao-Yin , Martin Javier San , Glorieux Francis

In children with XLH, high circulating levels of FGF23 cause hypophosphatemia with consequent rickets, skeletal deformities, and growth impairment. Conventional therapy consists of multiple daily doses of oral phosphate and active vitamin D (Pi/D). Burosumab is a fully human monoclonal antibody against FGF23 indicated for the treatment of XLH. In the active-control study CL301 (NCT02915705), 61 children with XLH (1–12 years old) were randomized (1:1) to receive subcutaneo...

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...

hrp0092p1-261 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology (1) | ESPE2019

Long-Term Urological and Psychosexual Outcome of Men Born with Hypospadias

Tack Lloyd , Van Hoecke Eline , Springer Alexander , Riedl Stefan , Tonnhofer Ursula , Weninger Julia , Hiess Manuela , Van Laecke Erik , Hoebeke Piet , Spinoit Anne-Françoise , Cools Martine

Introduction: According to EAU's guidelines, hypospadias (HS) repair is best performed between 6 and 18 months of age. Little is known about the long-term patient satisfaction or urological outcome following HS surgery.Aims: To examine the psychosexual and urological outcome of young adult men (16-21 years old) born with all forms of non-syndromic HS as compared to healthy controls, as well as patient and parental sa...