Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study.

CONTEXT: Somatrogon is a long-acting recombinant human growth hormone (rhGH) in development for once-weekly treatment of children with growth hormone deficiency (GHD). OBJECTIVE: We aimed to compare the efficacy and safety of once-weekly somatrogon with once-daily somatropin in prepubertal children with GHD. METHODS: In this 12-month, open-label, randomized, active-controlled, parallel-group, phase 3 study, participants were randomized 1:1 to receive once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. A total of 228 prepubertal children (boys aged 3-11 years, girls aged 3-10 years) with GHD, impaired height and height velocity (HV), and no prior rhGH treatment were randomized and 224 received ≥1 dose of study treatment (somatrogon: 109; somatropin: 115). The primary endpoint was annualized HV at month 12. RESULTS: HV at month 12 was 10.10 cm/year for somatrogon-treated subjects and 9.78 cm/year for somatropin-treated subjects, with a treatment difference (somatrogon-somatropin) of 0.33 (95% CI: -0.24, 0.89). The lower bound of the 2-sided 95% CI was higher than the prespecified noninferiority margin (-1.8 cm/year), demonstrating noninferiority of once-weekly somatrogon vs daily somatropin. HV at month 6 and change in height standard deviation score at months 6 and 12 were similar between both treatment groups. Both treatments were well tolerated, with a similar percentage of subjects experiencing mild to moderate treatment-emergent adverse events in both groups (somatrogon: 78.9%, somatropin: 79.1%). CONCLUSION: The efficacy of once-weekly somatrogon was noninferior to once-daily somatropin, with similar safety and tolerability profiles. (ClinicalTrials.gov no. NCT02968004).

Issues and trends in pediatric growth hormone therapy--an update from the GHMonitor observational registry.

The GHMonitor observational registry collates data on pediatric subjects receiving Saizen (recombinant human growth hormone (GH)) therapy. From January 2003 through August 2006, 1335 subjects were enrolled in the registry, approximately two-thirds of whom are male. The most common diagnosis in the registry is idiopathic growth hormone deficiency (58%). Most subjects in GHMonitor are receiving Saizen doses using a needle-free delivery device, the cool.click (73%). Mean height standard deviation scores show an improvement from -2.1 at screening to -1.1 following 3 years of Saizen therapy. To date, adverse events have been reported in 4% of subjects. Three serious adverse events were identified to be related to Saizen by the primary investigator: cellulitis at the injection site, behavioral problems/suicidal ideation, and enlargement of a craniopharyngioma. This article provides an update on data from the registry and briefly discusses topical and controversial issues in the treatment of pediatric patients requiring GH therapy.

Advances in the diagnosis and treatment of osteoporosis.

Although severely low bone density is relatively rare in the pediatric population, it can be a significant problem in many patients with chronic illness. As peak bone formation occurs during adolescence, it is crucial that pediatricians and other care providers for this patient population recognize the significance of attainment of adequate bone. Dietary intake of vitamin D and calcium should be optimized, and correction of underlying causes of poor bone density should occur whenever possible. Assessment of bone density is difficult, as each technology available has problems, and none of the technologies are well-associated with fracture risk in pediatric patients. Once diagnosis of severely low bone density is established, treatment options are limited and poorly studied. The benefits of bisphosphonate therapy appear to outweigh the risks in patients with low bone density and frequent fragility fractures, and it appears that most improvement with bisphosphonates occurs within the first 2 to 4 years. Evidence, however, is emerging that once off therapy, bone turnover remains decreased for at least several years. During that time, improvements in bone density are decreased. Many questions remain regarding duration of therapy with bisphosphonate therapy and the long-term effects on the children who receive this medication. Anabolic therapies may become important in the future, but there is currently extremely limited information regarding their use in pediatrics.

Growth hormone treatment improves growth and clinical status in prepubertal children with cystic fibrosis: results of a multicenter randomized controlled trial.

CONTEXT: This multicenter, randomized, controlled, crossover trial of prepubertal children with cystic fibrosis (CF) tests the hypotheses that recombinant human GH (rhGH) treatment 1) improves height, weight, lean mass, and bone content irrespective of baseline measures; 2) improves clinical status and quality of life; and 3) has continued effect after cessation after 1 yr of treatment. METHODS: Sixty-one prepubertal subjects (

The GHMonitorSM Registry: an update of the last three years.

The North American (US and Canada) GHMonitor was initiated to assess the safety and efficacy of Saizen (somatropin [recombinant human growth hormone for injection]) for growth disorders. Between 2003 and 2005, 1057 patients were enrolled in the registry; there were more males than females (67% vs 32%), the median age was 11.2 years, and most were Caucasian (80.9%). In the GHMonitor, the cool.click needle-free device (NFD) was the most widely used Saizen delivery device (73.8%), followed by needle and syringe (19.8%) and one.click (3.3%). At enrollment, most patients were recombinant human GH (rhGH) treatment-naïve (82.8%) and patients transitioning from prior rhGH therapy tended to choose cool.click NFD (67.1%), followed by needle and syringe (27.4%), and one.click(R) (1.8%). At screening, the most common diagnoses were idiopathic growth hormone deficiency (59%), idiopathic short stature (18%), neurosecretory dysfunction (6%), and Turner syndrome (3%). Patient characteristics included bone age that was delayed an average of one year relative to chronological age, a median BMI of 16.8 kg/m2, median height standard deviation score (SDS) -2.3, and median weight SDS -1.5. Eighteen of the forty reported adverse events (45%) were felt to be associated with Saizen. Most were mild and predominantly musculoskeletal complaints, although three were reported as serious.

Treatment of symptomatic pediatric osteoporosis with cyclic single-day intravenous pamidronate infusions.

OBJECTIVES: To examine the response to single-day intravenous pamidronate in a heterogeneous population with symptomatic osteoporosis. STUDY DESIGN: Patients (n = 18) 6 to 21 years of age, meeting treatment criteria were offered treatment with a single-day infusion of pamidronate every 3 months. Baseline and follow-up data were recorded and compared between persons with risk factors of progressive chronic illness or ongoing glucocorticoid usage (group 1) and persons with neither risk factor (group 2). We also examined the association between changes in urinary N-telopeptide percentile and spinal bone mineral density (BMD). RESULTS: Spinal BMD Z score increased in all patients after 6 months of treatment. Although patients had an average of 1.9 fractures in the year preceding treatment, only 2 patients had fractures once treatment began. No significant differences in baseline data were noted between the two groups. However, group 1 had significantly less gain in BMD (P =.04) than group 2. No evidence of growth impairment was seen, and no association between changes in urinary N-telopeptide percentile and changes in BMD were noted. CONCLUSIONS: Single-day intravenous infusion of pamidronate is efficacious and well tolerated in a heterogeneous group of pediatric patients with symptomatic osteoporosis.