setrusumab (UX143) / Novartis, Mereo Biopharma, Ultragenyx - LARVOL DELTA

The safety and efficacy of setrusumab in patients <18 years of age with osteogenesis imperfecta: 12-month results of the Phase 3 Orbit and Cosmic trials (ASBMR 2026) - No abstract available

Clinical • P3 data • Genetic Disorders

Artificial Intelligence for Evidence Synthesis of Emerging Biologics to Improve Skeletal Health in Osteogenesis Imperfecta: Systematic Review and Meta-Analysis. (PubMed, J Med Internet Res) - "We conducted a systematic review and meta-analysis of interventional trials of denosumab, setrusumab, teriparatide, romosozumab, and fresolimumab. These findings should be interpreted cautiously given the small and heterogeneous trial base. Taken together, our workflow presented how evidence synthesis may be scaled and operationalized in real-world rare disease research."

Journal • Retrospective data • Review • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Rare Diseases

Bone-tropic rAAV-mediated gene therapy ameliorates skeletal defects in Osteogenesis Imperfecta (ASGCT 2026) - "Furthermore, the recent failure of the anti- sclerostin antibody Setrusumab in phase 3 clinicals trials for OI underscores limited efficacy of osteoporosis drugs, as they cannot alter the course of collagen abnormalities...This approach offers a potential gene therapy platform for OI patients with a broad range of pathogenic COL1A2 variants. These findings support further preclinical and clinical investigation of gene therapy for autosomal dominant OI."

Gene therapy • Gene Therapies • Genetic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • COL1A1 • COL1A2

What's New in Osteogenesis Imperfecta. (PubMed, J Pediatr Soc North Am) - "Newer therapies-including denosumab, antisclerostin antibodies such as setrusumab, and mesenchymal stem cell transplantation-show promise but need further validation through randomized trials. Ongoing research continues to refine medical and surgical methods to improve function, quality of life, and long-term skeletal health for children with OI. (1)Multidisciplinary care is vital in caring for children with OI.(2)Medical optimization through nutrition, medications like bisphosphonates, vitamin D supplementation, and physical therapy is important for both preoperative and postoperative children with OI.(3)Intramedullary stabilization with telescoping or nontelescoping nails to protect the entire length of the bone is the mainstay of surgical treatment."

Journal • Review • Genetic Disorders • Musculoskeletal Diseases • Orthopedics • Transplantation • COL1A1 • COL1A2

ENGULF: Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta (clinicaltrials.gov) - P3 | N=69 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial primary completion date: Mar 2026 ➔ Oct 2025

Trial primary completion date • Genetic Disorders • Pediatrics • COL1A1 • COL1A2

Setrusumab vs Placebo for Osteogenesis Imperfecta (clinicaltrials.gov) - P2/3 | N=183 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial primary completion date: Mar 2026 ➔ Oct 2025

Trial primary completion date • Genetic Disorders • COL1A1

Artificial Intelligence in Evidence Synthesis: A Systematic Review and Meta-Analysis of Emerging Biologics for Improving Skeletal Health in Osteogenesis Imperfecta (ISPOR-EU 2025) - "OBJECTIVES: We aimed to systematically evaluate the effectiveness and safety of biologics in patients with Osteogenesis imperfecta (OI), integrating Artificial Intelligence (AI)-assisted assessment to enhance the rigor and efficiency of evidence synthesis. We conducted a systematic review and meta-analysis of trials assessing denosumab, setrusumab, teriparatide, and fresolimumab. Denosumab and setrusumab demonstrate promising efficacy in improving lumbar spine aBMD in OI, though current evidence does not support a definitive benefit of biologics in reducing fracture risk. GPT-4o supports evidence synthesis by improving screening efficiency and quality assessment, offering a scalable solution to reduce human workload. However, human oversight remains essential for tasks requiring contextual understanding and clinical reasoning."

Retrospective data • Review • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Pediatrics

ENGULF: Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta (clinicaltrials.gov) - P3 | N=69 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Jun 2026 ➔ Apr 2027 | Trial primary completion date: Dec 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Genetic Disorders • Pediatrics • COL1A1 • COL1A2

Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta (clinicaltrials.gov) - P2 | N=2 | Terminated | Sponsor: Ultragenyx Pharmaceutical Inc | Phase classification: P2b ➔ P2

Phase classification • Genetic Disorders

Sustained Reduction in Fracture Rate with Setrusumab in Osteogenesis Imperfecta: Data from Month 14 of Phase 2 of the Orbit Study [WITHDRAWN] (ENDO 2025) - P2/3 | "Taken together, these results support the data analyzed at 6 months of setrusumab therapy, confirming a robust and durable response to treatment in patients with OI.*. .*"

P2 data • Cardiovascular • Genetic Disorders • Musculoskeletal Diseases • Orthopedics

Consistent Reduction in Rate of Fracture with Setrusumab Therapy in Patients with Osteogenesis Imperfecta: Month 14 Data from Phase 2 of the Orbit Study (ESPE-ESE 2025) - P2/3 | "We report a meaningful reduction in the annualized rate of skeletal fractures (67%) with setrusumab therapy. Overall, the findings herein support those data reported after 6 months of setrusumab therapy, confirming the robust and durable response in participants with OI."

Clinical • P2 data • Cardiovascular • Genetic Disorders • Musculoskeletal Diseases • Orthopedics

Setrusumab vs Placebo for Osteogenesis Imperfecta (clinicaltrials.gov) - P2/3 | N=182 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Mar 2026 ➔ Apr 2027 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Genetic Disorders • COL1A1

Mereo BioPharma’s SWOT analysis: setrusumab, alvelestat drive rare disease stock potential (Investing.com) - "Mereo’s lead candidate, setrusumab, an anti-sclerostin monoclonal antibody, is currently in a Phase 3 study for the treatment of osteogenesis imperfecta (OI), commonly known as brittle bone disorder. The company is anticipating the second interim analysis (IA2) of this study in mid-2025...The company is nearing finalization of the Phase 3 trial design for alvelestat, a crucial step in securing a potential partnership....Mereo is actively engaged in discussions with potential partners for alvelestat, with a partnership potentially materializing in 2025."

Clinical protocol • Commercial • P3 data • Alpha-1 Antitrypsin Deficiency • Genetic Disorders

Mereo BioPharma Reports Full Year 2024 Financial Results and Provides Corporate Highlights (GlobeNewswire) - "Setrusumab (UX143): The Phase 3 portion of the Orbit Study is continuing to dose pediatric and young adult patients, with the second interim analysis expected mid-2025 and potential final analysis in the fourth quarter of 2025....Alvelestat (MPH-966): In the first quarter of 2025, the European Commission granted Orphan Designation to alvelestat for the treatment of AATD-LD. This designation followed a positive recommendation from the EMA Committee for Orphan Medicinal Products in January 2025....Total research and development ('R&D') expenses increased by $3.5 million from $17.4 million in 2023 to $20.9 million in 2024. The increase was primarily due to increases of $6.2 million and $2.6 million in R&D expenses for alvelestat and setrusumab, respectively..."

Commercial • Orphan drug • P3 data • Alpha-1 Antitrypsin Deficiency • Genetic Disorders

Clinical development of BPS804 for osteogenesis imperfecta: from failure to fruition? (PubMed, Expert Opin Investig Drugs) - No abstract available

Journal • Genetic Disorders • Musculoskeletal Diseases • Orthopedics

Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta (clinicaltrials.gov) - P3 | N=6 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Pediatrics

Non-invasive quantification of bone (re) modeling dynamics in adults with osteogenesis imperfecta treated with Setrusumab using timelapse HR-pQCT. (PubMed, J Bone Miner Res) - "We verified the accuracy of our method and then used it on longitudinal scans (baseline, 6, 12, 18 and 24 month) from 78 participants to assess bone formation and resorption induced by an anabolic (setrusumab) and anti-catabolic (zoledronic acid) treatments as part of the ASTEROID trial. This study identifies a timelapse method that minimizes measurement error, which can be used in future studies to improve the uniformity of results. This noninvasive imaging biomarker revealed dose dependent bone (re) modeling outcomes from one year of setrusumab treatment in adults with OI."

Journal • Genetic Disorders

Setrusumab in Pediatric Japanese Subjects with Osteogenesis Imperfecta (clinicaltrials.gov) - P3 | N=5 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Pediatrics

Setrusumab in Pediatric Japanese Subjects with Osteogenesis Imperfecta (clinicaltrials.gov) - P3 | N=5 | Not yet recruiting | Sponsor: Ultragenyx Pharmaceutical Inc

New P3 trial • Genetic Disorders • Pediatrics

Ultragenyx Receives Breakthrough Therapy Designation for Setrusumab (UX143) in Osteogenesis Imperfecta (GlobeNewswire) - "Ultragenyx Pharmaceutical Inc...announced that it has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for setrusumab (UX143) as a treatment to reduce the risk of fracture associated with osteogenesis imperfecta (OI) Type I, III, or IV in patients 2 years of age and older....The FDA’s decision is based on preliminary clinical evidence including the positive 14-month results from the Phase 2 portion of the Orbit study...and from the completed Phase 2b ASTEROID study."

Breakthrough therapy • Osteoporosis

Population Pharmacokinetics (PK) and PK/Pharmacodynamics Analyses to Select the Phase 3 Dose of Setrusumab in Pediatric Patients with Osteogenesis Imperfecta: Results From Phase 2 of the Orbit Study (ASBMR 2024) - No abstract available

Clinical • P2 data • P3 data • PK/PD data • Genetic Disorders • Pediatrics

Integrated Bone Biomarker Analyses to Define Setrusumab Mechanism of Action in Pediatric and Young Adult Subjects With Osteogenesis Imperfecta and to Inform Dose Selection in the Orbit Study (ASBMR 2024) - No abstract available

Biomarker • Clinical • Genetic Disorders • Pediatrics

Integrated Bone Biomarker Analyses to Define Setrusumab Mechanism of Action in Pediatric and Young Adult Subjects With Osteogenesis Imperfecta and to Inform Dose Selection in the Orbit Study (ASBMR 2024) - No abstract available

Biomarker • Clinical • Genetic Disorders • Pediatrics

Integrated Bone Biomarker Analyses to Define Setrusumab Mechanism of Action in Pediatric and Young Adult Subjects With Osteogenesis Imperfecta and to Inform Dose Selection in the Orbit Study (ASBMR 2024) - No abstract available

Biomarker • Clinical • Genetic Disorders • Pediatrics

Sustained Reduction in Fracture Rate in Patients with OI Treated with Setrusumab: Fourteen Month Data from Phase 2 of the Phase 2/3 Orbit Study (ASBMR 2024) - No abstract available

Clinical • Late-breaking abstract • P2/3 data • Musculoskeletal Diseases • Orthopedics