Safety and Efficacy of Lonapegsomatropin in Children With Growth Hormone Deficiency: enliGHten Trial 2-Year Results.

PURPOSE: The objectives of the ongoing, Phase 3, open-label extension trial enliGHten are to assess the long-term safety and efficacy of weekly administered long-acting growth hormone lonapegsomatropin in children with growth hormone deficiency. METHODS: Eligible subjects completing a prior Phase 3 lonapegsomatropin parent trial (heiGHt or fliGHt) were invited to participate. All subjects were treated with lonapegsomatropin. Subjects in the United States switched to the TransCon hGH Auto-Injector when available. Endpoints were long-term safety, annualized height velocity, pharmacodynamics [insulin-like growth factor-1 SD score (SDS) values], and patient- and caregiver-reported assessments of convenience and tolerability. RESULTS: Lonapegsomatropin treatment during enliGHten was associated with continued improvements in height SDS through week 104 in treatment-naïve subjects from the heiGHt trial (-2.89 to -1.37 for the lonapegsomatropin group; -3.0 to -1.52 for the daily somatropin group). Height SDS also continued to improve among switch subjects from the fliGHt trial (-1.42 at fliGHt baseline to -0.69 at week 78). After 104 weeks, the average bone age/chronological age ratio for each treatment group was 0.8 (0.1), showing only minimal advancement of bone age relative to chronological age with continued lonapegsomatropin treatment among heiGHt subjects. Fewer local tolerability reactions were reported with the TransCon hGH Auto-Injector compared with syringe/needle. CONCLUSIONS: Treatment with lonapegsomatropin continued to be safe and well-tolerated, with no new safety signals identified. Children treated with once-weekly lonapegsomatropin showed continued improvement of height SDS through the second year of therapy without excess advancement of bone age.

Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial.

CONTEXT: For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor adherence and suboptimal overall treatment outcomes. Lonapegsomatropin (TransCon hGH) is an investigational long-acting, once-weekly prodrug for the treatment of GHD. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of once-weekly lonapegsomatropin vs daily somatropin. DESIGN: The heiGHt trial was a randomized, open-label, active-controlled, 52-week Phase 3 trial (NCT02781727). SETTING: This trial took place at 73 sites across 15 countries. PATIENTS: This trial enrolled and dosed 161 treatment-naïve, prepubertal patients with GHD. INTERVENTIONS: Patients were randomized 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily. MAIN OUTCOME MEASURE: The primary end point was annualized height velocity (AHV) at week 52. Secondary efficacy end points included change from baseline in height SD scores (SDS). RESULTS: Least squares (LS) mean (SE) AHV at 52 weeks was 11.2 (0.2) cm/year for lonapegsomatropin vs 10.3 (0.3) cm/year for daily somatropin (P = 0.009), with lonapegsomatropin demonstrating both noninferiority and superiority over daily somatropin. LS mean (SE) height SDS increased from baseline to week 52 by 1.10 (0.04) vs 0.96 (0.05) in the weekly lonapegsomatropin vs daily somatropin groups (P = 0.01). Bone age/chronological age ratio, adverse events, tolerability, and immunogenicity were similar between groups. CONCLUSIONS: The trial met its primary objective of noninferiority in AHV and further showed superiority of lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naïve children with GHD.

A STRATIFIED CROSS-SECTIONAL CLUSTER MODEL SURVEY OF IODINE NUTRITION IN ARMENIA AFTER A DECADE OF UNIVERSAL SALT IODIZATION.

Objective: Iodine is a necessary nutrient for the synthesis of thyroid hormones and essential in human development. Being naturally deficient in iodine, Armenia launched a national universal salt iodization (USI) strategy in 2004. Although high rates of goiter continued to be reported, iodine status has not been studied since 2005. Therefore, this study sought to assess the current situation of population iodine nutrition in Armenia. Methods: We used a selective cross-sectional model to recruit three groups: school-age children (SAC), pregnant women (PW), and nonpregnant women of reproductive age (WRA) from each province. We collected casual urine and table salt samples from each participant, which were analyzed for iodine concentration. A repeat urine sample was collected in a subset of participants to adjust the results for within-person variation in iodine concentration. Group-wise urinary iodine concentrations (UICs) were compared with international reference criteria for iodine status. Results: Urine samples were collected from 1,125 participants from 13 different towns in Armenia; a total of 1,078 participants were included in the final analysis: 361 SAC (mean age, 10.5 years, 46.6% female), 356 PW (mean age, 26.1 years), and 361 WRA (mean age, 35.5 years). Population and geographically weighted median UIC were: SAC, 242 µg/L ([25th percentile] 203 to [75th percentile] 289 µg/L); PW, 226 µg/L (209 to 247 µg/L); WRA, 311 µg/L (244 to 371 µg/L). A total of 1,041 table salt samples were sufficient for laboratory analysis: 973 (93.4%) of the salt iodine measurements were within the national standard range of 40 ± 15 mg/kg. Conclusion: The results of household salt sampling indicated a successful USI strategy. While the present study did not achieve a truly representative sample of Armenia's population, the UIC results support the conclusion that iodine deficiency has not recurred and is not an underlying factor for any remaining high goiter prevalence in Armenia. Abbreviations: PW = pregnant women; SAC = school-age children; SI = salt iodine; UIC = urinary iodine concentration; USI = universal salt iodization; WHO = World Health Organization; WRA = women of reproductive age.

Constituent analysis of iodine intake in Armenia.

OBJECTIVE: We sought to assess the universal salt iodization (USI) strategy in Armenia by characterizing dietary iodine intake from naturally occurring iodine, salt-derived iodine in processed foods and salt-derived iodine in household-prepared foods. DESIGN: Using a cross-sectional cluster survey model, we collected urine samples which were analysed for iodine and sodium concentrations (UIC and UNaC) and household salt samples which were analysed for iodine concentration (SI). SI and UNaC data were used as explanatory variables in multiple linear regression analyses with UIC as dependent variable, and the regression parameters were used to estimate the iodine intake sources attributable to native iodine and iodine from salt in processed foods and household salt. SETTING: Armenia is naturally iodine deficient; in 2004, the government mandated a USI strategy. SUBJECTS: We recruited school-age children (SAC), pregnant women (PW) and non-pregnant women of reproductive age (WRA). RESULTS: From thirteen sites covering all provinces, sufficient urine and table salt samples were obtained from 312 SAC, 311 PW and 332 WRA. Findings revealed significant differences between groups: contribution of native iodine ranged from 81% in PW to 46% in SAC, while household salt-derived iodine contributed from 19% in SAC to 1% in PW. CONCLUSIONS: Differences between groups may reflect differences in diet. In all groups, household and processed food salt constituted a significant part of total iodine intake, highlighting the success and importance of USI in ensuring iodine sufficiency. There appears to be leeway to reduce salt intake without adversely affecting the iodine status of the population in Armenia.