Lonapegsomatropin-tcgd

Introduction: A 12-year-and-9-month-old non-Hispanic black male with a history of growth hormone deficiency, pituitary hypoplasia, prediabetes, obesity, hypertension, and hyperlipidemia was initiated on weekly growth hormone (lonapegsomatropin-tcgd) and then transiently developed symptomatic hyperglycemia to 500 mg/dL. We aimed to describe this medication’s effect. Case Presentation: He was born full term and appropriate for gestational age. He was referred to endocrinology at 3.5 years of age for short stature with a height SDS of −2.48. IGF-1 51.1 ng/mL and IGFBP-3 1.2 ng/mL were low. GH stimulation test noted baseline and peak GH of 0.1 ng/mL. MRI brain showed hypoplastic adenohypophysis, aplastic pituitary stalk, and ectopic neurohypophysis. There had been difficulty with adherence to daily GH over the following 9 years. BMI trajectory rose above 180% of the 95th percentile. By age 12, A1c was 6.6%. Metformin was started and increased to 1,000 mg twice daily. Subsequent A1c was 6.0%. Due to poor compliance with daily GH, at 12 years and 9 months, he was initiated on 22 mg (0.25 mg/kg/week) of weekly lonapegsomatropin-tcgd to improve compliance. The day after his first injection, he developed non-bloody, non-bilious emesis. He denied headaches and endorsed polyuria. Due to concern for increased intracranial pressure, he was sent to the emergency department; however, ophthalmologic exam was negative. Initial serum glucose was 500 mg/dL, then 336 mg/dL after 1-L normal saline. Hemoglobin A1c was 5.7%, urine glucose 3+ mg/dL, and urine ketones 2+ mg/dL. Venous pH of 7.379 and bicarbonate of 20.6 mmol/L ruled out diabetic ketoacidosis. Metformin was held during the hospitalization. Hyperglycemia rapidly improved with transient insulin administration. He received one dose of glargine 20 units. He was initiated on lispro carb ratio of 1:8 and correction factor 1:15 for target glucose 150 mg/dL. By day four, glucoses were below 100 mg/dL; lispro was discontinued, and he was discharged home. Weekly GH was discontinued with plans to resume daily GH therapy in several months. Conclusion: Lonapegsomatropin-tcgd offers the convenience of weekly rather than daily GH treatment; however, this patient developed a rapid increase in insulin resistance and hyperglycemia requiring insulin. The discrepancy between the glucose of 500 mg/dL and A1c of 5.7%, along with the rapid resolution of hyperglycemia, is further consistent with a medication side effect. Close glucose monitoring of patients initiated on weekly growth hormone is crucial, particularly in those with a history of prediabetes.

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.

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.

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.

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.