LB-OR02-Late-Breaking Oral Session- Clinical
Presentation Start Time: 11:45 AM
Room 210 (BCEC)
Somavaratan is a novel rhGH fusion protein (MW 119 kDa) with rapid absorption, delayed clearance and serum t1/2>100 hours (1). When administered subcutaneously, it has demonstrated the capacity to increase subnormal IGF-I levels into the normal range, in a dose dependent manner, for up to one month (2). In 2013, a multicenter, randomized, phase 1b/2a study was begun to evaluate treatment responses to somavaratan in pre-pubertal children with GHD. We present the results for the second year of treatment, completed in December 2015. Initially, 48 subjects participated in a single dose PK/PD study to establish pediatric doses, which were then tested in 64 subjects for 6 months at weekly, twice-monthly and monthly frequencies at a total dose of 5.0 mg/kg per month (NCT01718041). Sixty subjects remained on these doses in an extension study (NCT02068521). Based on growth and IGF-I responses, the cohort was then assigned to complete their second treatment year at a 3.5 mg/kg twice-monthly dose. IGF-I was measured by mass spectroscopy. Bone ages were interpreted by a central reader using the Fels method. Data are presented as mean ±SD. Twenty-four females and 33 males (mean age 7.8 years) were evaluable in Year 2. At screening, HT-SDS was -2.6±0.6, IGF-I SDS was -1.5±0.8 and maximal stimulated GH was 5.3±2.6 ng/mL. While on 3.5 mg/kg twice-monthly, the most recent values for IGF-I SDS were: 0.59±1.4 at peak (3-5 days after injection) and -0.47±1.1 for trough taken at the end of dosing cycle. Between 18 and 24 months, only 9 of 101 peak IGF-I SDS values exceeded 2.0. The percentage of subjects experiencing related adverse events (AEs) in Year 2 was 12.3%. Events in general were mild and transient. No new types of related AEs appeared during Year 2. Compared to Year 1, for 57 subjects with growth measurements in Year 2, height velocity (HV) was maintained with minimal change (8.08±2.2 vs. 7.83±2.3 cm/yr). Height SDS continued to improve: -2.6±0.6 at screening, -2.1±0.6 at the end of Year 1 and -1.6±0.7 at the end of Year 2. Bone age (BA) changes were commensurate with growth improvement. The difference between chronological age and BA (years) was 1.51±0.8 at screening, 1.35±0.9 at Year 1 and 1.04±1.0 at Year 2. In conclusion, in pre-pubertal children with moderate GHD, twice-monthly somavaratan treatment maintained IGF-I in the normal range without overexposure and provided continuing catch-up growth through the first 2 years. No new types of related AEs and no long-term safety events were observed in Year 2. An increase in somavaratan dose to 3.5 mg/kg twice-monthly has maintained HV in Year 2 to a level similar to that reported from the NCGS database for patients in their second year of therapy with a daily regimen at the standard US dose (3). The 3.5 mg/kg twice-monthly somavaratan dose is now used in the Phase 3 study and is anticipated to improve 1st year HV in treatment-naïve GHD children (NCT02339090).
(1) Cleland et al., J Pharm Sci. 2012;101(8):2744-54. (2) Moore et al., J Clin Endocrinol Metab. 2015 Dec 16; Epub ahead of print. (3) Kaplowitz et al., Int J Pediatr Endocrinol. 2013;2013(1):9.
Disclosure: GMB: Consultant, Versartis, Inc., Consultant, Versartis, Inc.. HJN: Study Investigator, Versartis, Inc.. BSM: Clinical Researcher, Alexion, Clinical Researcher, Endo Pharmaceuticals, Study Investigator, Genentech, Inc., Speaker Bureau Member, Genentech, Inc., Medical Advisory Board Member, Genentech, Inc., Medical Advisory Board Member, Novo Nordisk, Speaker Bureau Member, Novo Nordisk, Study Investigator, Novo Nordisk, Study Investigator, Orphan Reach/Tolmar, Medical Advisory Board Member, Sandoz, Consultant, Sandoz, Study Investigator, Sandoz, Medical Advisory Board Member, Versartis, Inc., Consultant, Versartis, Inc., Study Investigator, Versartis, Inc.. PYF: Investigator, Eli Lilly & Company, Investigator, Novo Nordisk, Investigator, Versartis, Inc.. DN: Contract Research Organization, Versartis, Inc.. EH: Employee, Versartis, Inc.. JLC: Consultant, Versartis, Inc.. Nothing to Disclose: WVM, GBK
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