BPS804 Anti‐Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial. (19th April 2017)

• Record Type: Journal Article
• Authors: Glorieux, Francis H; Devogelaer, Jean‐Pierre; Durigova, Michaela; Goemaere, Stefan; Hemsley, Sarah; Jakob, Franz; Junker, Uwe; Ruckle, Jon; Seefried, Lothar; Winkle, Peter J
• Is Part Of: Journal of bone and mineral research. Volume 32:Number 7(2017:Jul.)
• Page Start: 1496
• Page End: 1504
• Publication Date: 2017-04-19
• Subjects: ANTI‐SCLEROSTIN ANTIBODY -- CLINICAL TRIALS -- DXA -- OSTEOGENESIS IMPERFECTA -- WNT; Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.3143
• Languages: English
• ISSNs: 0884-0431

Abstract

ABSTRACT: 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.