ESPE Abstracts (2015) 84 LBP--1267

Safety and Efficacy of Long-Acting GH (VRS-317) in Children with GHD: Effects of Dose Change in the Second Treatment Year

George Brighta, Wayne V Mooreb, Huong Jil Nguyenc, Gad B Kletterd, Bradley S Millere, Patricia Y Fechnerf, David Ngg, Eric Humphrissa & Jeffrey L Clelanda

aVersartis, Inc., Menlo Park, California, USA; bChildren’s Mercy Hospital and University of Missouri–Kansas City, Kansas City, Missouri, USA; cSierra Medical Research, Clovis, California, USA; dMary Bridge Children’s Hospital, Tacoma, Washington, USA; eUniversity of Minnesota Masonic Children’s Hospital, Minneapolis, Minnesota, USA; fSeattle Children’s Hospital, Seattle, Washington, USA; gResearch Point Global, Inc., Austin, Texas, USA

Background: VRS-317, a novel fusion protein of rhGH exhibiting delayed clearance, serum half-life generally >100 h, and potential for once monthly dosing, was previously evaluated in a 6-month phase 1b/2a study of weekly, twice monthly or monthly dosing (5.0 mg/kg per month) in prepubertal GHD children (n=64).

Objective and hypotheses: We evaluated whether increased VRS-317 dose from 12 to 18 months can offset the decrease in height velocities commonly seen during the 2nd year of daily rhGH treatment.

Method: In an ongoing long-term safety extension study, 63 subjects received an increased dose of VRS-317 (3.5 mg/kg, twice monthly). Peak IGF1 SDS and mean height velocities were compared before and after increased dose.

Results: 56 subjects completed 18 months of treatment. Mean age at Month 18 was 9.28 years; all but two subjects remain prepubertal. Increasing the twice monthly dose from 2.5 to 3.5 mg/kg increased mean peak IGF1 SDS from −0.30±1.2 to 0.32±1.6 (paired t-test, P=0.007); the number of peak IGF1 SDS >2.0 was limited to three values total for all subjects. Increased dosing appeared to stabilize height velocity: during the initial 12 months of treatment, mean height velocity was 7.9±2.1 and 8.5±2.1 cm/year for 5 mg/kg monthly and 2.5 mg/kg twice monthly dosing, respectively, compared with 8.1±2.4 and 8.3±1.8 cm/year (annualized), respectively, after 18 months (3.5 mg/kg twice monthly). Only mild and transient drug-related AEs were observed (n=9 patients after 12 months; n=7 patients after 18 months). No new or unexpected AEs occurred. Injection site discomfort decreased with time on treatment, with only four subjects reporting discomfort after 18 months.

Conclusion: Increasing VRS-317 dose at the start of the 2nd year of treatment to 3.5 mg/kg twice monthly (phase 3 dose) led to in an increase in mean peak IGF1 SDS and stabilization of mean height velocity, without changing the safety profile.