FDA Grants Breakthrough Therapy Designation to Setrusumab for Osteogenesis Imperfecta

Setrusumab (UX143; Ultragenyx Pharmaceutical, Inc) has received Breakthrough Therapy Designation from the FDA.¹ It is a treatment to reduce the risk of fracture connected with osteogenesis imperfecta (OI) type 1, 3, or 4 in patients 2 years of age and older.¹

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OI includes a group of genetic disorders that effect bone metabolism and occur in about 60,000 individuals, with no approved treatment options. Approximately 85% to 90% of cases are associated with genetic variants in the COL1A1 or COL1A2 genes, which result in reduced or abnormal collagen and changes in the bone metabolism. The collagen changes in OI lead to increased bone fragility, which can cause an increased number of fractures. Additionally, individuals with OI can experience a lack of production of new bone and excess bone resorption that can cause a decrease in bone mineral density, bone fragility, and weakness. Other challenges include bone deformities, abnormal spine curvature, pain, decreased mobility, and short stature, according to study authors.¹

"FDA designation of setrusumab as a breakthrough therapy emphasizes the seriousness of osteogenesis imperfecta and the impact of this disease on people and their families affected by this disorder,” said Eric Crombez, MD, chief medical officer at Ultragenyx, in a news release.¹

As a fully human monoclonal antibody, setrusumab reduces a negative regulator of bone formation known as sclerostin. This blocking is aimed to increase new bone formation, bone mineral density, and bone strength in OI, according to study authors.¹

The FDA granted the designation based on positive preliminary results from the phase 2 ORBIT study that assessed the impact of setrusumab on clinical fracture rate among individuals 5 to 25 years of age. The study included 24 individuals who were randomly assigned to receive setrusumab at 1 or 2 doses that were then used to determine the dosing for the phase 3 trial.^1,2

The results showed that individuals with OI who were treated with setrusumab had significant reduction in fractures by 67% with at least 14 months of follow-up. Further results found ongoing and meaningful improvements in lumbar spine bone mineral density (BMD) at 12 months without reports of plateau.²

“All indications are that setrusumab is having the effect we hoped for, safely reducing the incidence of fractures and improving BMD in patients with OI,” said Gary S. Gottesman, MD, professor of Pediatrics and Medicine at the Washington University School of Medicine, in a news release. “The anti-sclerostin antibody appears effective even after a year, and remarkably, patients continue to make measurable gains, suggesting we will see an ongoing response over the long term.”²

The study authors noted that findings suggest that setrusumab could offer rapid and clinically meaningful decrease in fracture rate in individuals with OI.^1,2

“The designation is also recognition of the significant clinical benefit observed in the phase 2 portion of the ORBIT study and supports our work to expeditiously bring this investigational therapy to patients who currently have no approved treatment option,” Crombez said, in a news release.¹

REFERENCES

1. Ultragenyx Receives Breakthrough Therapy Designation for Setrusumab (UX143) in Osteogenesis Imperfecta. Ultagenyx. News release. October 7, 2024. Accessed October 7, 2024. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-receives-breakthrough-therapy-designation-setrusumab.

2. Ultragenyx and Mereo BioPharma Announce New Phase 2 Data from Phase 2/3 Orbit Study Demonstrating Sustained Reductions in Fracture Rates Following Treatment with Setrusumab (UX143) in Patients with Osteogenesis Imperfecta (OI). Ultagenyx. News release. October 7, 2024. Accessed October 7, 2024. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-and-mereo-biopharma-announce-new-phase-2-data-phase.