BPS804 Anti-Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial.

This 21-week, open-label, phase 2a trial aimed to evaluate the pharmacodynamics and safety of multiple, escalating infusions of BPS804, a neutralizing, anti-sclerostin antibody, in adults with moderate osteogenesis imperfecta (OI). Patients received BPS804 (three escalating doses each separated by 2 weeks [5, 10, and 20 mg/kg]) or no treatment (reference group). The primary efficacy endpoints were mean changes from baseline to day 43 in: procollagen type 1 N-terminal propeptide (P1NP), procollagen type 1 C-terminal propeptide (P1CP), bone-specific alkaline phosphatase (BSAP), osteocalcin (OC), and type 1 collagen cross-linked C-telopeptide (CTX-1). Mean change from baseline to day 141 in lumbar spine areal bone mineral density (aBMD) was also assessed. BPS804 safety and tolerability were assessed every 2 weeks. Overall, 14 adults were enrolled (BPS804 group: n = 9, mean age 30.7 years, mean aBMD Z-score -2.6; reference group, n = 5, mean age 27.4 years, mean aBMD Z-score -2.2). In the BPS804 group, P1NP, P1CP, BSAP, and OC were increased by 84% (p < 0.001), 53% (p = 0.003), 59% (p < 0.001), and 44% (p = 0.012), respectively, versus baseline (reference: P1NP, +6% [p = 0.651]; P1CP, +5% [p = 0.600]; BSAP, -13% [p = 0.582]; OC, -19% [p = 0.436]). BPS804 treatment downregulated CTX-1 by 44% from baseline (reference: -7%; significance was not tested for this biomarker), and increased aBMD by 4% (p = 0.038; reference group: +1%; p = 0.138). BPS804 was generally well tolerated. There were 32 adverse events reported in nine patients; none was suspected to be treatment-related. There were no treatment-related fractures. BPS804 stimulates bone formation, reduces bone resorption, and increases lumbar spine aBMD in adults with moderate OI. This paves the way for a longer-term, phase 3 trial into the efficacy, safety, and tolerability of BPS804 in patients with OI. © 2017 American Society for Bone and Mineral Research.