Treatment Burden of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Randomized Study.

Context: Somatrogon is a long-acting recombinant human growth hormone treatment developed as a once-weekly treatment for pediatric patients with growth hormone deficiency (GHD). Objective: Evaluate patient and caregiver perceptions of the treatment burden associated with the once-weekly somatrogon injection regimen vs a once-daily Somatropin injection regimen. Methods: Pediatric patients (≥3 to <18 years) with GHD receiving once-daily somatropin at enrollment were randomized 1:1 to Sequence 1 (12 weeks of once-daily Somatropin, then 12 weeks of once-weekly somatrogon) or Sequence 2 (12 weeks of once-weekly somatrogon, then 12 weeks of once-daily Somatropin). Treatment burden was assessed using validated questionnaires completed by patients and caregivers. The primary endpoint was the difference in mean overall life interference (LI) total scores after each 12-week treatment period (somatrogon vs Somatropin), as assessed by questionnaires. Results: Of 87 patients randomized to Sequence 1 (n = 43) or 2 (n = 44), 85 completed the study. Once-weekly somatrogon had a significantly lower treatment burden than once-daily Somatropin, based on mean overall LI total scores after somatrogon (8.63) vs Somatropin (24.13) treatment (mean difference -15.49; 2-sided 95% CI -19.71, -11.27; P < .0001). Once-weekly somatrogon was associated with greater convenience, higher satisfaction with treatment experience, and less LI. The incidence of treatment-emergent adverse events (TEAEs) for Somatropin and somatrogon was 44.2% and 54.0%, respectively. No severe or serious AEs were reported. Conclusion: In pediatric patients with GHD, once-weekly somatrogon had a lower treatment burden and was associated with a more favorable treatment experience than once-daily Somatropin.

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.

Switching to Weekly Lonapegsomatropin from Daily Somatropin in Children with Growth Hormone Deficiency: The fliGHt Trial.

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.

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.

Congenital hypothyroidism and the second newborn metabolic screening in Colorado, USA.

OBJECTIVE: To evaluate the effectiveness of a second newborn screening for congenital hypothyroidism (CH). METHODS: All infants born in Colorado, USA, from July 1996 through June 2004 had a total thyroxine measured with secondary thyroid stimulating hormone determination. RESULTS: The number of first and second newborn screens completed was 494,324 and 471,877, respectively. The first screen identified 185 cases of CH (incidence of 1:2,703). The second screen identified an additional 42 cases. Overall, the incidence based on both the first and second screenings was 1:2,174. The false negative rate for the first screen was 15.6%. In the absence of a second screen, one infant with CH out of every 11,111 babies screened would have been missed. The addition of the second screen increased the cost-per-case identified from dollars 6,108 to dollars 9,730. CONCLUSIONS: With only one newborn screen for CH, the number of missed cases is significant and higher than previously reported.

Total cholesterol and high-density lipoprotein levels in pediatric subjects with type 1 diabetes mellitus.

This study reports serum lipid levels in 682 children with type 1 diabetes mellitus. We found that 3.5% of the subjects had a high-density lipoprotein (HDL) cholesterol level < 35 mg/dL, 15.4% had a total cholesterol (TC) level>200 mg/dL, and 18.6% were abnormal for either HDL or TC, compared with prevalences of 5.7%, 11.2%, and 16.3%, respectively, reported in the National Health and Nutrition Examination Survey 2001-02. Hemoglobin A1c value was significantly related to TC and non-HDL cholesterol levels.

Increased incidence and severity of diabetic ketoacidosis among uninsured children with newly diagnosed type 1 diabetes mellitus.

OBJECTIVES: (a) To determine the incidence and severity of diabetic ketoacidosis (DKA) and (b) to stratify according to insurance status at the initial diagnosis of type 1 diabetes (T1DM). RESEARCH DESIGN AND METHODS: Subjects included children <18 yr who presented with new-onset T1DM from January 2002 to December 2003 and were subsequently followed at the Barbara Davis Center. Insurance status and initial venous pH were obtained. RESULTS: Overall, 383 subjects presented with new-onset T1DM and 359 (93.7%) were enrolled. Forty-three (12.0%) of these children were uninsured and 40 (11.1%) had Medicaid. One hundred and two (28.4%) subjects presented with DKA. When compared to the insured subjects, uninsured subjects had a significantly increased risk of presenting with DKA [odds ratios (OR): 6.19, 95% CI 3.04-12.60, p < 0.0001], as well as presenting with severe DKA, defined as venous pH <7.10 (OR: 6.09, 95% CI 3.21-11.56, p < 0.0001). There were no differences, however, between the insured and Medicaid subjects in their probability of presenting with DKA or severe DKA. The risk of presenting with DKA (as well as with severe DKA) was the highest among patients <4 yr old. CONCLUSIONS: At the time of initial diagnosis, uninsured patients were more likely to present with DKA than insured patients. Furthermore, when the uninsured subjects presented with DKA, the condition tended to be more severe and life-threatening. A potential explanation is that uninsured subjects may delay seeking timely medical care, thereby presenting more critically ill, whereas insured subjects may have their T1DM diagnosed earlier.

Missed insulin meal boluses and elevated hemoglobin A1c levels in children receiving insulin pump therapy.

OBJECTIVE: To identify possible causes of suboptimal glycemic control (ascertained by hemoglobin A1c [HbA1c] level) in youths using insulin pump therapy. METHODS: Forty-eight youths who were receiving insulin pump therapy for > or =6 months, and who were using insulin pumps and blood glucose meters with data that could be downloaded at our facility, are included in this cross-sectional study. Possible causes of suboptimal glycemic control were evaluated by using 4 information sources: 1) insulin pump data downloads; 2) glucose meter data downloads; 3) patient/family questionnaire about insulin bolusing habits, eating habits, exercise, and blood glucose testing habits; and 4) a physician questionnaire. Physicians completed the questionnaire during the patient interview after reviewing the downloaded information and discussing these results with the patient/family. RESULTS: The mean (+/- standard deviation) age of participants was 15.3 (+/-3.0) years (range: 7-20 years), and the mean (+/- standard deviation) duration of type 1 diabetes and continuous subcutaneous insulin infusion was 8.2 (+/-4.0) and 1.9 (+/-1.0) years, respectively. Patients who missed <1 bolus per week had a mean (95% confidence interval) HbA1c level of 8.0% (7.7, 8.3), whereas those who missed > or =1 mealtime boluses per week had a mean HbA1c level (95% confidence interval) of 8.8% (8.6, 9.1). No significant relationships were found between HbA1c levels in males and females, the amount of exercise per week, or bolusing before insulin pump disconnection for exercise. Although not significant, a trend was found for those who missed <1 bolus per week to perform more blood glucose tests per day and for those who bolused before a meal rather than after to have lower HbA1c levels. Significant correlations were found between HbA1c levels and the number of missed mealtime boluses per week (r =.414) and mean blood glucose levels (r =.70). CONCLUSION: Missed mealtime insulin boluses seem to be the major cause of suboptimal glycemic control in youths with diabetes receiving continuous subcutaneous insulin infusion therapy.