Mecasermin biosimilar (Merck Sharp & Dohme Corp.)

The Global Increlex® Growth Forum Database (IGFD) Registry monitors real-world effectiveness and safety of recombinant human IGF-1 (rhIGF-1; Increlex® [mecasermin]) treatment in children and adolescents with severe growth failure due to severe primary IGF-I deficiency (SPIGFD).

To report characteristics, effectiveness, and safety data from patients receiving rhIGF-1 treatment who achieved near-adult height (NAH), and determine factors that predict height gain to NAH.

Descriptive analyses of patients included in the Global IGFD Registry (NCT00903110) who achieved NAH are reported for the overall population, treatment-naïve prepubertal (NPP) patients, and patients with Laron syndrome. Linear regression analyses of height gain to NAH are also reported.

One hundred and two patients enrolled in the Global IGFD Registry achieved NAH at data cut-off (April 20, 2023). Mean age at rhIGF-1 treatment initiation was 11.8 years; median treatment duration was 3.9 years. Mean (SD) height SD score (HtSDS) gain from rhIGF-1 initiation to NAH was 0.9 (1.1). In NPP patients, mean (SD) HtSDS gain was 1.4 (1.0). Almost half of NPP patients reached NAH within the normal range. Despite improved height in patients with Laron syndrome, only 10.5% reached NAH within the normal range; 3 patients with Laron syndrome were NPP. Treatment naivety was predictive of height gain in the overall NAH population. Safety data aligned with previous reports.

In a real-world setting, despite patients with SPIGFD initiating rhIGF-1 treatment at a relatively advanced age, rhIGF-1 treatment resulted in improved NAH. The greatest improvements in height outcomes were observed in NPP patients.

NCT00903110.

Preterm birth affects about 10% of all live births with many resultant health challenges, including metabolic bone disease of prematurity (MBDP), which is characterized by elevated alkaline phosphatase, suppressed phosphate, and deficient skeletal development. Because of the lack of an animal model, very little is known about bone structure, strength, and quality after preterm birth. This study investigated the utility of a pig model to replicate clinical features of preterm birth, including MBDP, and sought to determine if early postnatal administration of IGF-1 was an effective treatment. Preterm pigs, born by caesarean section at 90% gestation, were reared in intensive care facilities (respiratory, thermoregulatory, and nutritional support) and compared with sow-reared term pigs born vaginally. Preterm pigs were systemically treated with vehicle or IGF-1 (recombinant human IGF-1/BP-3, 2.25 mg/kg/d). Tissues were collected at postnatal days 1, 5, and 19 (the normal weaning period in pigs). Most bone-related outcomes were affected by preterm birth throughout the study period, whereas IGF-1 supplementation had almost no effect. By day 19, alkaline phosphatase was elevated, phosphate and calcium were reduced, and the bone resorption marker C-terminal crosslinks of type I collagen was elevated in preterm pigs compared to term pigs. Preterm pigs also had decrements in femoral cortical cross-sectional properties, consistent with reduced whole-bone strength. Thus, the preterm pig model replicates many features of preterm bone development in infants, including features of MBDP, and allows for direct interrogation of skeletal tissues, enhancing the field’s ability to examine underlying mechanisms.