ESPE Abstracts

Norditropin® was approved for children with short stature due to NS in Japan in 2017. The aim of this post-marketing surveillance study was to evaluate long-term safety and effectiveness of Norditropin^® for the approved indication. This real-world non-interventional study (NCT03435627) was conducted February 2018–January 2022. Seventy patients enrolled: 35 received Norditropin^® after study initiation (new patients); 35 were previously randomised to 0.033 or 0.066 mg/kg/day (0.23 or 0.47 mg/kg/week, respectively) during a 4-year clinical trial of Norditropin^® for NS (NCT01927861) and continued treatment in this study (existing patients, for whom baseline was start of the prior trial). Treatment duration was up to 4 and 8.5 years for new and existing patients, respectively. All patients who received Norditropin^® at least once during the study comprised the full analysis set (FAS). All FAS patients with a height value at baseline and ≥1 follow-up visit comprised the effectiveness analysis set (EAS). Males comprised 60.0% and 65.7% of new and existing FAS patients, respectively. At study start, most patients in both groups received an average dose range of 0.03–<0.04 mg/kg/day (0.2−<0.3 mg/kg/week). Mean (SD) IGF-I SDS was −0.47 (1.66) for new patients after 3.5 years’ treatment. For existing patients, mean (SD) IGF-I SDS was 0.04 (1.45) at start of this study and −0.46 (1.03) after 8 years’ treatment. In the EAS, mean (SD) change from baseline in height SDS was 1.01(0.52)/0.92(0.31) for new patients after 3.5 years, and 1.10(0.99)/1.31(0.80) for existing patients after 8 years, according to Japanese/NS standards, respectively. Adult height was reached by 16 and 28 for new and existing patients, respectively. In the FAS, four new patients experienced five adverse drug reactions (ADR) and one new patient experienced one serious adverse event (SAE). Five existing patients experienced one ADR each and three existing patients experienced one SAE each. One existing patient with cardiomyopathy who experienced an SAE (arrhythmia) died during the study; Norditropin^® causality was judged as ‘unlikely’ by the physician and ‘impossible to assess’ by the sponsor. In this real-world study, Norditropin^® effectively improved height outcomes and was well tolerated in Japanese children with NS. Dose optimisation is important to maintain improvements in height outcomes. For patients with NS and cardiomyopathy receiving Norditropin®, careful monitoring is advised. No new safety issues were identified.