Endocrine Abstracts

Efficacy of rhGH for treatment of pediatric GH deficiency (PGHD) may depend on several variables at treatment initiation (age, body weight, height velocity (HV), IGF-I SDS, skeletal maturation, GHmax), but may be compromised by poor adherence to required daily injections. Somavaratan is a novel, long-acting rhGH fusion protein that demonstrated clinically meaningful improvements in HV and IGF-I concentration in PGHD patients. Over 200 pre-pubertal GHD subjects have enrolled in somavaratan trials to date, including 137 in the Phase 3 noninferiority VELOCITY trial comparing somavaratan vs daily rhGH. In the randomized Phase 1b/2a VERTICAL study in pre-pubertal children with GHD, primary determinants of Year 1 HV included age at treatment initiation and GHD severity. To achieve a valid basis of comparison of efficacy outcomes across trials (VELOCITY, VERTICAL, VISTA (long-term safety)), distribution of clinical characteristics known to affect HV should be similar between treatment arms (somavaratan vs daily rhGH) and between trials. The same primary efficacy endpoint (HV) and similar eligibility criteria were used across trials. Stratification for Phase 3 randomization (somavaratan vs daily rhGH) was based on region, expected age, and expected baseline IGF-I SDS. In VELOCITY (n=104 somavaratan; n=32 daily rhGH), mean±S.D. baseline ages were 7.07±2.0 vs 7.03±2.4 years, respectively, mean GHmax 5.77±2.6 vs 5.87±2.5 ng/ml, mean height-SDS −2.76±0.7 vs −2.64±0.7, mean IGF-I SDS -1.72±0.7 vs −1.87±0.9, and mean bone ages 5.28±1.9 vs 5.29±2.2 years. In VERTICAL (N=64), mean age was 7.8±2.4 years, mean height-SDS −2.6±0.6, mean IGF-I SDS −1.7±0.8, and mean bone age 6.4±2.4 years. No clinically meaningful differences in baseline characteristics were noted between trials, or between VELOCITY treatment arms. Collectively, similar populations were achieved between trials by use of consistent eligibility and stratification procedures. This allowed balanced treatment arms for clinical characteristics that may influence the primary efficacy outcome, thereby achieving a valid basis of comparison between trial populations.