Ultragenyx's Setrusumab Faces Setback in Phase 3 Trial for Brittle Bone Disease

Ultragenyx Pharmaceutical Inc. and partner Mereo BioPharma encountered a hurdle in their phase 3 Orbit study evaluating setrusumab (UX143) for osteogenesis imperfecta, commonly known as brittle bone disease. The monoclonal antibody failed to meet the efficacy threshold for early study termination at the second interim analysis, prompting a significant market reaction.

Trial Continuation Despite Early Setback

The phase 3 Orbit study, involving 159 pediatric and young patients with osteogenesis imperfecta, will continue to its final analysis following recommendations from the data monitoring committee. Ultragenyx CEO Emil Kakkis, M.D., Ph.D., stated, "Based on the feedback we hear from investigators and families who participated in the studies, we are confident that increasing bone mass leads to stronger bone, less fractures, and improved physical abilities."

While the company had hoped for an early conclusion to the study, Kakkis expressed optimism about receiving results around the end of this year. The data monitoring committee confirmed that setrusumab "demonstrates an acceptable safety profile," supporting the decision to continue the trial.

Market Response and Analyst Perspectives

The news of the missed interim efficacy threshold sparked a sharp decline in Ultragenyx's stock, which fell 23% to $31.96 in pre-market trading on Thursday from the previous day's closing price of $41.44. However, William Blair analysts characterized this market reaction as "severely overdone" in a July 10 note.

Despite the setback, analysts maintain a positive outlook on the drug's potential. "While it is unfortunate that the Orbit study did not achieve its statistical significance threshold at the second interim analysis, we ... still believe there is a high likelihood that the final analysis in the fourth quarter will be positive given there will be a longer duration of follow-up and a lower threshold for statistical significance," the William Blair analysts noted.

Background and Previous Results

Setrusumab, which inhibits sclerostin (a negative regulator of bone formation), showed promise in earlier studies. Two years ago, phase 2 data demonstrated a 67% reduction in bone fractures among 24 patients with at least six months of follow-up.

Ultragenyx acquired the ex-Europe rights to setrusumab from Mereo BioPharma in 2020 for an upfront payment of $50 million. The ongoing phase 3 trial aims to build on these earlier positive results and potentially provide a new treatment option for patients with osteogenesis imperfecta.