Ultragenyx Pharmaceutical Inc. and Mereo BioPharma Group plc presented secondary endpoint data on UX143 (setrusumab) from the Phase 2b ASTEROID study for the Treatment of Osteogenesis Imperfecta (OI). Data were presented at the American Society for Bone and Mineral Research (ASBMR) 2021 Annual Meeting in an oral presentation by Suzanne Jan de Beur, M.D., an associate professor of medicine at The Johns Hopkins University School of Medicine and president of ASBMR. Previously reported analyses of pre-specified endpoints in the Phase 2b ASTEROID study demonstrated a clear, dose-dependent, statistically significant bone-building effect at multiple anatomical sites in adult patients with OI that was consistent across all subtypes of OI studied, including Types I, III and IV. This effect was determined by evaluating areal bone mineral density (BMD) over baseline at the lumbar spine, as measured by DXA and reaching 8.97% at 12 months in the highest dose cohort (p<0.001).

The data also show a statistically significant and consistent improvement in bone strength (stiffness) over baseline at the wrist and tibia measured by Finite Element Analysis (FEA) in both medium and high dose cohorts (p<0.05). There was also a statistically significant improvement in bone strength (failure load) at the wrist at the highest dose (p<0.01). New data presented at ASBMR demonstrate that treatment with UX143 resulted in dose-dependent increase in P1NP serum levels, a marker of bone formation, and decrease in CTx serum levels, a marker of bone resorption, confirming the mechanism of action of sclerostin inhibition.

These changes peaked at month one and declined thereafter, an expected effect based on data from prior clinical studies of sclerostin antibodies tested in osteoporosis. Observed improvements in BMD were continuous, with comparable gains achieved in the first and second 6 months of treatment in the high dose group despite temporal changes in biomarkers. Top-line 12-month data from the ASTEROID study were reported in November 2019, with full data, including secondary endpoint analyses, reported in January 2020.