Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Sep 2;39(9):1215-1228.
doi: 10.1093/jbmr/zjae112.

Setrusumab for the treatment of osteogenesis imperfecta: 12-month results from the phase 2b asteroid study

Francis H Glorieux  1 , Bente Langdahl  2   3 , Roland Chapurlat  4 , Suzanne Jan De Beur  5 , Vernon Reid Sutton  6 , Kenneth E S Poole  7 , Kathryn M Dahir  8 , Eric S Orwoll  9 , Bettina M Willie  10   11 , Nicholas Mikolajewicz  10   11 , Elizabeth Zimmermann  10   11 , Seyedmahdi Hosseinitabatabaei  10   11 , Michael S Ominsky  12 , Chris Saville  13 , James Clancy  14 , Alastair MacKinnon  14 , Arun Mistry  14 , Muhammad K Javaid  15
Affiliations
Clinical Trial

Setrusumab for the treatment of osteogenesis imperfecta: 12-month results from the phase 2b asteroid study

Francis H Glorieux et al. J Bone Miner Res. .

Erratum in

Abstract

Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or 20 mg/kg setrusumab doses or placebo by monthly intravenous infusion during a 12-mo treatment period. Participants initially randomized to the placebo group were subsequently reassigned to receive setrusumab 20 mg/kg open label. Therefore, only results from the 2, 8, and 20 mg/kg double-blind groups are presented herein. The primary endpoint of Asteroid was change in distal radial trabecular volumetric bone mineral density (vBMD) from baseline at month 12, supported by changes in high-resolution peripheral quantitative computed tomography micro-finite element (microFE)-derived bone strength. A total of 110 adults were enrolled with similar baseline characteristics across treatment groups. At 12 mo, there was a significant increase in mean (SE) failure load in the 20 mg/kg group (3.17% [1.26%]) and stiffness in the 8 (3.06% [1.70%]) and 20 mg/kg (3.19% [1.29%]) groups from baseline. There were no changes in radial trabecula vBMD (p>05). Gains in failure load and stiffness were similar across OI types. There were no significant differences in annualized fracture rates between doses. Two adults in the 20 mg/kg group experienced related serious adverse reactions. Asteroid demonstrated a beneficial effect of setrusumab on estimates of bone strength across the different types of OI and provides the basis for additional phase 3 evaluation.

Keywords: bone mineral density; osteogenesis imperfecta; rare disease; sclerostin; setrusumab.

Plain language summary

Osteogenesis imperfecta (OI), is a rare disorder affecting patients’ bones causing pain and an increased chance of the bone breaking. Setrusumab is a possible treatment for OI being studied in a clinical trial called Asteroid. The goal of Asteroid was to determine which dose of setrusumab helped adults with OI the most: 2, 8, or 20 mg/kg. Researchers looked at the density of patients’ bones and estimated how strong their bones were before setrusumab and again after 12 mo of treatment to see how they improved with treatment. Researchers could compare these improvements to see which dose of setrusumab helped patients the most. Patients on the highest dose of setrusumab (20 mg/kg) experienced improvements in the density of their arm bones (radius) and leg bones (tibia) after 12 mo. The strength of these bones also improved. The density of other bones including the spine, hip, and the overall skeleton (total body) also improved with treatment. Of patients who had side effects after receiving setrusumab, most were mild or moderate intensity. Overall, setrusumab improved the bones of patients with OI with no serious safety concerns. More studies will include even more patients to see how setrusumab can improve their bones.

PubMed Disclaimer

Conflict of interest statement

F.H.G.: Grant and Travel Support: Mereo BioPharma, Kiowa Kirin Co., Ultragenyx Pharmaceutical Inc.; Member of the Boards of the Osteogenesis Imperfecta Foundation USA and of the Canadian Osteogenesis Imperfecta Society.

B.L.: Research Support: Mereo BioPharma; Grant Support, Advisory Board: Amgen; Advisory board, Speaker: UCB, Gedeon-Richter; Speaker: Eli Lilly, Astra-Zeneca, Gilead.

R.C.: Consultant: AbbVie, Amgen, Biocon, Bristol Myers Squibb, Galapagos, Novartis, Pfizer, UCB; Speaker: AbbVie, Amgen, Eli Lilly, Galapagos, Kyowa Kirin Co., UCB; Travel Support: AbbVie, Amgen, Bristol Myers Squibb; Grant Support: UCB.

S.J.D.B.: Research Support: Mereo BioPharma; Research support, Consultant, Advisory Board: Ultragenyx; Advisory Board: Amgen.

V.R.S.: Research and Travel Support, Advisory Board: Mereo BioPharma; Medical Advisory Council: Osteogenesis Imperfecta Foundation.

K.E.S.P.: Consultant and Grant Support: Mereo BioPharma; Consultant and Speaker: Amgen, UCB through Cambridge Enterprise (CE); all fees donated on receipt by CE to various charities.

K.M.D.: Research Support: Mereo BioPharma Consultant and Grant Support: Kiowa Kirin Co., Ultragenyx Pharmaceutical Inc.; Alexion AstraZeneca; Grant Support: SoftBones.

E.S.O.: Research and Grant Support: Mereo BioPharma; Consultant: Ultragenyx Pharmaceutical Inc, Sanofi, Angitia, Quince.

B.M.W.: Consultant, Advisory Board, Research Support: Mereo BioPharma.

N.M.: Advisory Board, Research Support: Mereo BioPharma.

E.Z.: Research Support: Mereo BioPharma.

J.C., A.M., A.M., Employees: Mereo BioPharma.

M.S.O.: Employee: Ultragenyx Pharmaceutical Inc.

C.S.: Employee of ICON.

M.K.J.: Consultant, Speaker, Advisory Board: Mereo BioPharma; Amgen, UCBB, Kyowa Kirin Hakin, AbbVie, Sanofi, Grant support; Amgen, Kyowa Kirin Hakin, UCB Clinical Lead, Advisory Board: Brittle Bone Society.

Figures

Figure 1
Figure 1
Changes in bone strength by microFE after 12 mo of setrusumab, A. Radius bone strength, B. Tibial bone strength.
Figure 2
Figure 2
Changes in vBMD from baseline at month 12, A. Radius vBMD, B. Tibial vBMD.
Figure 3
Figure 3
Areal bone mineral density by dual-energy x-ray absorptiometry scan.
Figure 4
Figure 4
Changes in biomarkers of bone formation (A-C) and resorption (D) from baseline, A. Procollagen type 1 N-terminal propeptide, B. osteocalcin, C. bone-specific alkaline phosphatase, D. collagen cross-linked C-telopeptide type 1.
See this image and copyright information in PMC

References

    1. Marini JC, Forlino A, Bachinger HP, et al. Osteogenesis imperfecta. Nat Rev Dis Primers. 2017;3(1):17052. 10.1038/nrdp.2017.52 - DOI - PubMed
    1. van Dijk FS, Cobben JM, Kariminejad A, et al. Osteogenesis imperfecta: a review with clinical examples. Mol Syndromol. 2011;2(1):1–20. 10.1159/000332228 - DOI - PMC - PubMed
    1. Ishikawa Y, Bachinger HP. A molecular ensemble in the rER for procollagen maturation. Biochim Biophys Acta. 2013;1833(11):2479–2491. 10.1016/j.bbamcr.2013.04.008 - DOI - PubMed
    1. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16(2):101–116. 10.1136/jmg.16.2.101 - DOI - PMC - PubMed
    1. Lindahl K, Astrom E, Rubin CJ, et al. Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta. Eur J Hum Genet. 2015;23(8):1042–1050. 10.1038/ejhg.2015.81 - DOI - PMC - PubMed

Publication types