FP24-5 BA058, a Novel Human PTHrP Analog, Restores Bone Density and Increases Bone Strength At the Spine and Femur in Osteopenic Rats

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP24-New Mechanisms in Bone Biology: From Cells to Genetics, & Mice to Men
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:05 AM
Room 121 (Moscone Center)

Poster Board SUN-200
Gary Hattersley*1, Elisabeth Lesage2, Aurore Varela2 and Susan Smith2
1Radius Health, Inc, Cambridge, MA, 2Charles River, Senneville, QC, Canada
BA058 is an analog of hPTHrP (1-34) currently in Phase 3 of clinical development for the treatment of post-menopausal osteoporosis. The objectives of this study were to determine the effect of BA058 after 1-year of treatment on bone mass and bone strength in ovariectomized (OVX) skeletally mature Sprague-Dawley rats. Six-month old virgin female rats (18/group) were randomly assigned to five groups. Four groups were OVX and one group underwent Sham surgery (ovaries intact). Treatment was initiated following a 3-month bone depletion period. Animals received daily subcutaneous injections of vehicle (Sham and OVX controls), or BA058 at 1, 5 or 25 µg/kg/day for 1 year. Blood and urine samples were analyzed for calcium and markers of bone turnover (P1NP, CTx, OC, DPD). aBMD was measured at the lumbar spine and the femur by DXA, vBMD was measured at the proximal tibia metaphysis by pQCT, and bone strength parameters were evaluated at the lumbar vertebrae and the femur. At the end of the bone depletion period, OVX animals showed a loss in aBMD of 6‑8% at the lumbar spine and distal femur and a loss of 6% at the proximal tibia. Within 13-weeks of treatment with BA058, BMC and BMD increased in a dose-proportional manner at clinically relevant sites, spine and femur, with restoration of vBMD at the tibia metaphysis, to or above pre-OVX and Sham values. After 1 year, marked increases in bone mass and geometry measured by DXA and pQCT were observed with BA058, reaching 73, 164 and 428%, at 1, 5 and 25 µg/kg/day respectively, for trabecular BMD at the tibia metaphysis, compared to OVX controls. Increases in bone mass were associated with dose-related increases in bone strength parameters. With 25 µg/kg/day an increase in peak load of approximately 90, 49 and 172% was observed at the femur diaphysis, femoral neck and lumbar vertebrae, respectively, compared to OVX controls. P1NP and OC were markedly increased by BA058 without any effect on resorption markers (DPD and CTx). BA058 treatment did not increase serum calcium. In conclusion, BA058 offers a number of potentially important advantages as a new treatment for osteoporosis, including the ability to rapidly build new bone.

Disclosure: GH: Employee, Radius Health. EL: Employee, Charles River. AV: Employee, Charles River. SS: Employee, Charles River.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm