PMID- 35263755 OWN - NLM STAT- MEDLINE DCOM- 20220808 LR - 20220928 IS - 1663-2826 (Electronic) IS - 1663-2818 (Print) IS - 1663-2818 (Linking) VI - 95 IP - 3 DP - 2022 TI - Switching to Weekly Lonapegsomatropin from Daily Somatropin in Children with Growth Hormone Deficiency: The fliGHt Trial. PG - 233-243 LID - 10.1159/000524003 [doi] AB - INTRODUCTION: The phase 3 fliGHt Trial evaluated the safety and tolerability of once-weekly lonapegsomatropin, a long-acting prodrug, in children with growth hormone deficiency (GHD) who switched from daily somatropin therapy to lonapegsomatropin. METHODS: This multicenter, open-label, 26-week phase 3 trial took place at 28 sites across 4 countries (Australia, Canada, New Zealand, and the USA). The trial enrolled 146 children with GHD, 143 of which were previously treated with daily somatropin. All subjects received once-weekly lonapegsomatropin 0.24 mg human growth hormone/kg/week. The primary outcome measure was safety and tolerability of lonapegsomatropin over 26 weeks. Secondary outcome measures assessed annualized height velocity (AHV), height standard deviation score (SDS), and IGF-1 SDS at 26 weeks. RESULTS: Subjects had a mean prior daily somatropin dose of 0.29 mg/kg/week. Treatment-emergent adverse events (AEs) reported were similar to the published AE profile of daily somatropin therapies. After switching to lonapegsomatropin, the least-squares mean (LSM) AHV was 8.7 cm/year (95% CI: 8.2, 9.2) at Week 26 and LSM height SDS changed from baseline to Week 26 of +0.25 (95% CI: 0.21, 0.29). Among switch subjects, the LSM for average IGF-1 SDS was sustained at Weeks 13 and 26, representing an approximate 0.7 increase from baseline (prior to switching from daily somatropin therapy). Patient-reported outcomes indicated a preference for weekly lonapegsomatropin among both children and their parents. CONCLUSIONS: Lonapegsomatropin treatment outcomes were as expected across a range of ages and treatment experiences. Switching to lonapegsomatropin resulted in a similar AE profile to daily somatropin therapy. CI - The Author(s). Published by S. Karger AG, Basel. FAU - Maniatis, Aristides K AU - Maniatis AK AD - Rocky Mountain Pediatric Endocrinology, Centennial, Colorado, USA. FAU - Nadgir, Ulhas AU - Nadgir U AD - Center of Excellence in Diabetes and Endocrinology, Sacramento, California, USA. FAU - Saenger, Paul AU - Saenger P AD - NYU Langone Health, New York University Langone, New York, New York, USA. FAU - Reifschneider, Kent L AU - Reifschneider KL AD - Hospital of The Kings Daughters, Norfolk, Virginia, USA. FAU - Abuzzahab, Jennifer AU - Abuzzahab J AD - Children's Minnesota, Saint Paul, Minnesota, USA. FAU - Deeb, Larry AU - Deeb L AD - TMH Physician Partners Metabolic Health Center Pediatric Endocrinology, Tallahassee, Florida, USA. FAU - Fox, Larry A AU - Fox LA AD - Nemours Children's Health, Jacksonville, Florida, USA. FAU - Woods, Katie A AU - Woods KA AD - Doernbecher Children's Hospital at Oregon Health and Sciences University, Portland, Oregon, USA. FAU - Song, Wenjie AU - Song W AD - Ascendis Pharma, Incorporated, Palo Alto, California, USA. FAU - Mao, Meng AU - Mao M AD - Ascendis Pharma, Incorporated, Palo Alto, California, USA. FAU - Chessler, Steven D AU - Chessler SD AD - Ascendis Pharma, Incorporated, Palo Alto, California, USA. FAU - Komirenko, Allison S AU - Komirenko AS AD - Ascendis Pharma, Incorporated, Palo Alto, California, USA. FAU - Shu, Aimee D AU - Shu AD AD - Ascendis Pharma, Incorporated, Palo Alto, California, USA. FAU - Casella, Samuel J AU - Casella SJ AD - Children's Hospital at Dartmouth, Lebanon, New Hampshire, USA. FAU - Thornton, Paul S AU - Thornton PS AD - Cook Children's Medical Center, Fort Worth, Texas, USA. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study DEP - 20220309 PL - Switzerland TA - Horm Res Paediatr JT - Hormone research in paediatrics JID - 101525157 RN - 0 (lonapegsomatropin) RN - 12629-01-5 (Human Growth Hormone) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - 9002-72-6 (Growth Hormone) SB - IM MH - Body Height MH - Child MH - *Drug Substitution MH - *Dwarfism, Pituitary/drug therapy MH - Growth Disorders/drug therapy MH - *Growth Hormone/therapeutic use MH - *Human Growth Hormone/therapeutic use MH - Humans MH - Insulin-Like Growth Factor I/therapeutic use PMC - PMC9501775 OTO - NOTNLM OT - Growth hormone OT - Growth hormone deficiency OT - Growth hormone replacement therapy OT - Lonapegsomatropin OT - Long-acting growth hormone OT - TransCon human growth hormone COIS- A.K.M. has received research funding and is an Advisory Board Consultant for Ascendis Pharma, Novo Nordisk, OPKO, and Pfizer and is a speaker for Ascendis Pharma and Novo Nordisk. P.S. has been a speaker for Ascendis Pharma and Novo Nordisk and has received research funding from Ascendis Pharma, OPKO, Novo Nordisk, and Aeterna Zentaris, and is a member of the editorial board of Hormone Research in Paediatrics. K.L.R. has received research funding from Ascendis Pharma, is a speaker for Ascendis, and serves as a board member of The Human Growth Foundation. J.A. has received research funding from Ascendis Pharma, Novo Nordisk, Lumos, Soleno, Rhythm, and Saniona, and has served as a consultant for Consynance Therapeutics and Rhythm. K.A.W. has served as a consultant for Ascendis Pharma. S.J.C. has received research funding from Ascendis Pharma. W.S., M.M., S.D.C., A.S.K., and A.D.S. are employees of Ascendis Pharma, Inc. P.S.T. has received research funding from Ascendis Pharma, Novo Nordisk, Pfizer, and OPKO. U.N., L.D., and L.A.F. have nothing to declare. EDAT- 2022/03/10 06:00 MHDA- 2022/08/09 06:00 PMCR- 2022/03/09 CRDT- 2022/03/09 20:08 PHST- 2021/10/01 00:00 [received] PHST- 2022/02/24 00:00 [accepted] PHST- 2022/03/10 06:00 [pubmed] PHST- 2022/08/09 06:00 [medline] PHST- 2022/03/09 20:08 [entrez] PHST- 2022/03/09 00:00 [pmc-release] AID - 000524003 [pii] AID - hrp-0095-0233 [pii] AID - 10.1159/000524003 [doi] PST - ppublish SO - Horm Res Paediatr. 2022;95(3):233-243. doi: 10.1159/000524003. Epub 2022 Mar 9.