SAN FRANCISCO, CA -- (Marketwired) -- 06/16/13 -- Versartis, Inc. today presented the first results from its pediatric clinical trial of VRS-317, the company's proprietary long-acting form of recombinant human growth hormone (rhGH). "A Phase 1b/2a Study of a New Long-acting Growth Hormone (VRS-317) in Pre-pubertal Children with Growth Hormone Deficiency (GHD)" was accepted as a "late breaker" poster, and was presented at ENDO 2013: The Endocrine Society's 95th Annual Meeting & Expo in San Francisco by Versartis Vice President of Medical Affairs George M. Bright, MD. At present, the only approved growth hormone treatments require daily injections. VRS-317 is expected to provide up to once-monthly dosing.
"The human clinical data presented today shows that a single dose of VRS-317 was very well tolerated in children with GHD and that the drug levels and IGF-I responses increase in intensity and duration with increasing dose," stated Dr. Bright. "These results confirm and extend the VRS-317 results recently published on adult GHD patients and allow VRS-317 to be optimized for up to once-monthly dosing."
The VRS-317 VERTICAL Trial
The Versartis Trial In Children to Assess Long-Acting Growth Hormone (VERTICAL) study is being conducted in approximately 30 U.S. pediatric endocrinology centers and will enroll up to 72 naïve-to-treatment, pre-pubertal children with GHD that was documented by auxologic criteria and two GH stimulation tests. The VERTICAL trial of VRS-317 consists of two stages: a single ascending dose stage (Phase 1b) to determine the safety, PK and PD of VRS-317 doses and to enable selection of dose regimens used in the repeat dose stage (Phase 2a) to obtain 6 month height velocity results.
In Phase 1b, the PK and PD (IGF-I) responses over a 30 day period are determined following a single, subcutaneous dose of VRS-317 at up to 6 ascending dose levels. Safety Review Committee meetings are held before each dose escalation to review collected data against protocol-specified stopping criteria. VRS-317 dose selection for Phase 2a will be based on safety and IGF-I responses from Phase 1b. Following dose selection, subjects will be randomized to a maximum of three doses or dose regimens for the determination of 6 month height velocities. VRS-317 dosing began at 0.80 mg/kg, a dose shown to be safe and well tolerated in GHD adults in the previously completed trial, with planned dose increases to 1.20 mg/kg, 1.80 mg/kg, 2.70 mg/kg, 4.00 mg/kg and up to 6.00 mg/kg (equivalent to 4.8, 7.4, 11.1, 16.7, 24.7 and 37.0 mcg rhGH per kg per day taken for 30 days). In the United States, the typical dose of daily rhGH in children with GHD is approximately 40 mcg/kg/day. Thus, the VRS-317 doses studied in this trial are all below the typical amount of daily rhGH utilized for these patients.
Top Line Results
To date, 32 subjects (21M, 9F) with mean (SD) age 7.3 (2.1) yrs have been studied in the first four dose cohorts (8 per cohort). At screening, mean (SD) HT-SDS was -2.7 (0.6), weight was 18.3 (4.4) kg and IGF-I SDS was -1.73 (0.6). VRS-317 plasma concentrations reach a maximum at a mean time of 3 days post-dose, are linearly proportional to dose and remain detectable for up to 30 days from a single dose in all subjects tested. Maximal changes in IGF-I SDS occur between 2 to 7 days after a single dose on Day 1. The amplitude and duration of IGF-I responses increase with increasing VRS-317 dose. At 2.70 mg/kg of VRS-317, the IGF-I SDS was maintained above baseline through Day 30 in 6 of 8 patients and through Day 22 in the remaining 2 patients. The prolonged IGF-I responses do not come at the expense of over-exposure to high IGF-I levels, where only a single value of IGF-I SDS in one patient has exceeded +2 (2.11). Related adverse events have been reported in 12 subjects to date and all have been mild and transient with no serious or unexpected adverse events reported.
Conclusions
Single doses of up to 2.70 mg/kg of VRS-317 administered to 32 pre-pubertal GHD children are safe and well tolerated. In addition, dose proportional increases in VRS-317 levels and IGF-I responses were observed, indicating the ability to select doses and dose regimens for up to once per month dosing.
NOTE: The company's first double-blind, placebo-controlled, single ascending dose study of VRS-317 in growth hormone deficient adults was published ahead of print in the Journal of Clinical Endocrinology & Metabolism (JCEM) on April 12, 2013 [doi:10.1210/jc.2013-1437] and was published in final print in the June issue of JCEM [J Clin Endocrinol Metab, June 2013, 98(6):2595-2603] (Yuen JCEM). As reported in this paper, single SC doses of VRS-317 were safe, well tolerated and increased IGF-I levels in a dose-dependent manner. At the highest dose tested (0.80 mg/kg, equivalent to 4.8 mcg/kg/day over 30 days), the mean VRS-317 t1/2 was 131 hrs and mean IGF-I SDS was maintained above -1.5 for three weeks after a single SC dose.
About Versartis
Versartis, Inc. is a biotechnology company developing therapeutics for the treatment of endocrine disorders. The company's lead product candidate is VRS-317, a novel long-acting form of human growth hormone. VRS-317 is currently being investigated for safety and efficacy in pediatric GHD patients for up to once monthly dosing. Versartis is pursuing the development of new therapeutic proteins utilizing the proprietary Amunix half-life extension technology (XTEN). XTEN is a novel hydrophilic sequence of natural amino acids and is expressed as a fusion protein with a therapeutically active peptide or protein. New compounds developed by Versartis using the XTEN technology are expected to provide improved therapeutic outcomes such as enhanced efficacy/compliance, fewer side effects, prolonged half-life (up to monthly dosing), as well as low-cost production and enhanced stability. Further information on Versartis can be found at www.versartis.com.
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