IMPE Abstracts

Objective: To evaluate the long-term safety and effectiveness of daily growth hormone (Norditropin®; somatropin) in Japanese children with short stature due to Noonan syndrome (NS).

Methods: This post-marketing, prospective, non-interventional, Japanese multicentre study (NCT03435627) was conducted in a real-world setting from February 2018 to April 2022. Among the 70 enrolled patients, 35 received Norditropin® only after initiation of this study (naïve patients); 35 had completed a 4-year clinical trial of Norditropin® in NS (NCT01927861) (non-naïve patients, for whom baseline was the start of the clinical trial). Treatment duration was up to 4 years (naïve) or 8.5 years (non-naïve). The full analysis set (FAS) included all patients receiving Norditropin® at least once during the study. The effectiveness analysis set (EAS) included all FAS patients with a height value at baseline and at least one follow-up visit.

Results: Sixty percent and 65.7% of naïve and non-naïve FAS patients, respectively, were male. Baseline mean (SD) values for naïve/non-naïve patients were: age 7.9 (3.8)/5.2 (2.0) years; height 111.25 (18.79)/95.77 (11.56) cm; height standard deviation score (SDS): –2.928 (0.711)/–3.324 (0.661). In the EAS, height SDS (Japanese and NS standards), height velocity (HV) and HV SDS were significantly different and greater than baseline at 1 year and subsequent years (up to 3.5/8 years for height SDS [ P<0.001], up to 2/4 years for HV [ P<0.001], and up to 3/8 years for HV SDS [ P<0.05], for naïve/non-naïve patients, respectively).

In the FAS, one naïve patient reported one SAE (road traffic accident; not a serious ADR). Three non naïve patients reported an SAE: arrhythmia, odontoma and ventricular tachycardia, the first two being serious ADRs. The patient with arrhythmia died during the study; causality of Norditropin® was judged as ‘unlikely’ by the physician and ‘impossible to assess’ by the sponsor, and the patient had arrhythmia and hypertrophic cardiomyopathy at baseline. Among 70 patients, four reported AEs of cardiovascular disease.

Conclusions: In children with NS and short stature, long-term Norditropin® therapy effectively improved height outcomes. No new safety issues were identified. Cardiac disease is common in NS and the approved labelling states that Norditropin® should be administered with care in patients with heart disease.