Ultragenyx Pharmaceutical Inc. has just announced the first dosing in their Phase 2/3 trial investigating setrusumab (UX143) as a treatment for osteogenesis imperfecta (OI) patients. This trial is called Orbit, and it is building off the Phase 2b trial called ASTEROID which lasted 12 months. This trial demonstrated there was a dose-dependent effect of setrusumab on bone density and formation at many sites.
The ASTEROID trial examined adult patients. The Orbit study will study the same medication in patients ages 5 to 25. Ultragenyx is also working to develop another study which will examine this therapy in patients ages 2-5. The Phase 3 Orbit study is anticipated to start near the end of 2022.
Osteogenesis Imperfecta
OI refers to a group of rare conditions which affect the metabolism of the bone. Most patients with the condition have a mutation in the COL1A2 or COL1A1 gene. These mutations lead to altered bone metabolism and abnormal or reduced collagen production.
Patients face bone weakness and fragility, low bone mass, breakdown of bone, and an inadequate production of new bone. Patients with the condition can present with spine curvature, short stature, bone deformity, and decreased mobility. Pain is a common symptom all patients face, as is bone brittleness, which leads to repeat fractures.
Unfortunately, there have yet to be any treatments approved for this condition. That is what makes this investigation all the more important.
Setrusumab
Setrusumab is a human monoclonal antibody. It inhibits sclerotin which is a protein responsible for inhibiting bone-forming cell activity. By blocking the effects of sclerotin, bone formation, bone strength, and bone mineral density are all increased. Additionally, the treatment decreases the rates of bone resorption.
Mouse models of this therapy first showcased its ability to stimulate the production of bone and improve bone density. As a result, bone fragility was decreased, and the rate of fractures was minimized drastically.
Orbit
It is especially important to study this therapy in younger children because this population has a higher fracture risk. Not only is the risk higher, but there is a greater chance for longterm consequences from these fractures.
This trial is a global investigation that will include patients with OI subtypes 1, 111, and 1v.
This trial has two portions – a Phase 2 and a Phase 3. The Phase 2 portion will include 36 randomized patients. One randomized group will receive placebo, and the other two groups will receive a specific dose of the therapy. Through this portion of the trial, researchers will be able to determine the optimal dose of setrusumab.
The second component of this trial – the Phase 3 investigation – will include 195 patients. These patients will be randomized to either be given placebo or setrusumab at the optimal dose. The primary endpoint of this investigation will be the reduction in fracture rate.
After 24 months of the investigation, all patients will move to an open-label extension so that they can receive the therapy.
You can read more about this trial and investigative treatment for OI here.
