|By Marketwired .||
|September 22, 2013 02:30 AM EDT||
MILAN, ITALY -- (Marketwired) -- 09/22/13 -- Versartis, Inc. today released the latest positive results from the company's ongoing VERTICAL clinical trial of VRS-317, its proprietary long-acting form of recombinant human growth hormone (rhGH), at the 9th Joint Meeting of Paediatric Endocrinology in Milan. The most recent data from this trial in pediatric patients were presented by George M. Bright, MD, Versartis Vice President of Medical Affairs, in an oral discussion titled "A Phase 1b/2a Study of a New Long-acting Growth Hormone (VRS-317) in Pre-pubertal Children with Growth Hormone Deficiency (GHD)." All currently approved growth hormone drugs require daily injections and consequently pose considerable challenges to patients with GHD. In contrast, VRS-317 is being developed to provide up to once-monthly dosing and promises to improve patients' ability to adhere to their therapy regimen and to improve their overall treatment outcomes.
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. Results from the recently completed Phase 1b dose-escalating stage of the study were reported by Dr. Bright.
Dr. Bright commented, "The latest data from the Phase 1b demonstrated that a single dose of VRS-317 was very well tolerated in children with GHD and that we were able to safely raise IGF-I to the levels associated with good catch-up growth while using a reduced dosing frequency. Therefore, the data presented today provide strong support for the continued study of up to once-monthly dosing in the next stage of our trial, which was initiated earlier this month. This study will further determine the 3-month and 6-month height velocities in these GHD patients."
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.
In Phase 1b, the PK and PD (IGF-I) responses over a 30 day period were determined following a single, subcutaneous dose of VRS-317 at 6 ascending dose levels. Safety Review Committee meetings were held before each dose escalation to review collected data against protocol-specified stopping criteria. 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 dose increases to 1.20 mg/kg, 1.80 mg/kg, 2.70 mg/kg, 4.00 mg/kg and 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 amount of daily rhGH typically prescribed for these patients. VRS-317 dose selection for Phase 2a was based on safety and IGF-I responses from Phase 1b. Following Phase 2a dose selection, subjects are now being dosed in each of three dose cohorts for the determination of 3-month and 6-month height velocities.
Top Line Results
In the Phase 1b portion of the trial, 48 subjects (27M, 21F) with mean (SD) age 7.2 (2.2) yrs were studied in 6 dose cohorts (8 per cohort). At screening, mean (SD) HT-SDS was -2.7 (0.6), weight was 18.0 (4.6) kg and IGF-I SDS was -1.8 (0.7). VRS-317 plasma concentrations reach a maximum at a mean time of 3 days post-dose, are 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 14 days after a single dose on Day 1. The amplitude and duration of IGF-I responses increase with increasing VRS-317 dose. The increase in average IGF-1 SDS over 30 days was also proportional to dose and sufficient to support up to once-monthly dosing of VRS-317. Importantly, 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 each of two patients has exceeded +2. All related adverse events that have been reported were mild and transient, with no serious or unexpected adverse events reported.
Single doses of VRS-317 from 0.8 to 6.0 mg/kg were safe and well tolerated when administered to 48 pre-pubertal children with GHD. In addition, dose proportional increases in VRS-317 levels and IGF-I responses were observed, indicating the flexibility for selecting doses and dose regimens of up to once-per-month dosing. Consequently, VRS-317 is a long-acting rhGH with the potential for up to monthly-dosing intervals in children with GHD.
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.