ESPE Abstracts (2014) 82 P-D-1-3-171

Safety and Efficacy Results of a 6 Month, Randomized, Multi-Center Trial of a Novel Long-Acting rhGH (VRS-317) in Naive to Treatment, Pre-Pubertal Children with GH Deficiency

George M Brighta, Wayne V Mooreb, H Q Nguyenc, Gad B Kletterd, Bradley S Millere,f, Douglas G Rogersg, Eric Humphrissa & Jeffrey Clelanda

aVersartis, Inc, Redwood City, California, USA; bChildren’s Mercy Hospital, Kansas City, Missouri, USA; cSierra Medical Research, Clovis, CA, USA; dSwedish Pedaitric Specialty Clinics, Seattle, Washington, USA; eUniversity of Minnesota, Minneapolis, Minnesota, USA; fAmplatz Children’s Hospital, Minneapolis, Minnesota, USA; gCleveland Clinic, Cleveland, Ohio, USA

Background: VRS-317, a novel fusion protein of rhGH, was safe and well tolerated in single dose studies of adults and children with growth harmone deficiency (GHD).

Objectives: Conduct a 6-month study to determine the safety, tolerability, height velocity and IGF1 response in GHD children.

Methods: 64 subjects were randomized into three arms to evaluate monthly, semi-monthly and weekly dosing.

Results: At VRS-317 doses equivalent to daily rhGH of ~ 30 μg rhGH/kg per day, repeat dosing of VRS-317 in phase 2a is safe and well tolerated in pre-pubertal GHD children and maintained mean IGF1 increases over baseline and within the therapeutic range without IGF1 overexposure. There have been no related serious adverse events or unexpected adverse events. Other related adverse events have been primarily mild and transient and of the type expected when rhGH is initiated in children naïve to rhGH treatment. With more than 1000 injections administered to date, discomfort at injection sites has been reported in a minority of patients and has been mild and transient. Nodule formation or lipoatrophy has not been observed at injection sites. Peak IGF1 levels have been the greatest with monthly dosing but did not exceed 3 S.D. and in only three cases transiently exceeded 2 S.D. Mean trough IGF1 SDS levels remain above baseline at day 30 in all dosing groups. After 2 months of dosing, peak IGF1 levels have been generally higher than after the first dose, suggesting that repeat VRS-317 dosing may augment IGF1 responses. The mean annualized 3-month height velocities from GHD children in the phase 2a were comparable to the historical age-matched controls administered a comparable dose of daily rhGH (33 μg rhGH/kg per day).

Conclusions: Overall, results to date in the phase 2a clinical trial of GHD children indicate that VRS-317 has a comparable safety and efficacy profile to historical studies of daily rhGH administered at comparable doses.