Once-weekly somapacitan in children with Noonan syndrome: randomized controlled phase 3 trial.

OBJECTIVE

Daily growth hormone (GH) injections are indicated for the treatment of short stature in children with Noonan syndrome, which presents a treatment burden for the child and their parents/caregivers. Somapacitan is a long-acting, reversible albumin-binding GH, developed for once-weekly administration. The objective of this study is to evaluate efficacy, safety, and tolerability of somapacitan versus daily GH in children living with Noonan syndrome.

DESIGN

REAL8 (NCT05330325) is a multinational, multicenter, randomized, open-labeled, active comparator, phase 3 basket study including four non-GH deficiency indications comprising a 52-week main phase and 104-week extension. Here, we present 52-week results from the REAL8 Noonan syndrome substudy.

METHODS

Seventy-seven GH-treatment-naïve, prepubertal boys (aged 2.5-11 years) and girls (aged 2.5-10 years) with Noonan syndrome were randomized 2:1 to somapacitan 0.24 mg/kg/week or daily GH 0.050 mg/kg/day, administered subcutaneously.

RESULTS

The primary endpoint, estimated mean annualized height velocity at week 52, was 10.4 cm/year for somapacitan versus 9.2 cm/year for daily GH (estimated treatment difference [ETD]: 1.2, 95% CI [0.32; 2.03]), confirming noninferiority and demonstrating superiority of somapacitan compared to daily GH (P < .01). The estimated change from baseline to week 52 in height standard deviation score was 1.07 and 0.75 for somapacitan and daily GH, respectively (ETD: 0.32, 95% CI [0.16; 0.48]). Somapacitan was well tolerated and had a similar safety profile to daily GH.

CONCLUSIONS

Once-weekly somapacitan was confirmed as noninferior and demonstrated superiority to daily GH in HV after 52 weeks of treatment in treatment-naïve children living with Noonan syndrome. Similar safety profiles and tolerability were observed for both groups.

CLINICAL TRIAL REGISTRATION: NCT05330325.