Eric Crombez, MD, Chief Medical Officer of Ultragenyx, discusses the latest results from the Phase 2/3 Orbit Study targeting osteogenesis imperfecta.
Transcription:
Orbit is the name we have given to our ongoing phase 2/3 study. We have been talking about the data from the phase 2 study for a little while now. What’s exciting is we now have had patients in study long enough that we can also look at fracture rates. Originally the phase 2 portion of the study, like all phase 2 studies, was really designed to establish initial safety and really select a dose that you bring forward for your phase 3, your pivotal trial. The decision on dose selection was really based on biomarkers, particularly P1NP, that is a form of procollagen and an important biomarker because P1NP is what’s cleaved off as collagen is being laid down to make new bones. Really a direct relationship to the laying down of new bones. That’s important.
Then also looking at bone mineral density and how the change in biomarkers reflects the increase in bone mineral density. That allowed us to select the dose of 20 milligrams per kilogram to take forward in phase 3. Again, now that we have all 24 patients enrolled in the study at least the six-month time point looking at fracture data.
We have previously spoken about the changes in P1NP, a key biomarker here. P1NP levels do peak at around one month but do stay elevated in these patients as they’re laying down new bone. We do see the correlation with improvement in bone mineral density and that is improvement itself, but then also comparison to Z scores and seeing a good correlation in the change in biomarker to improvement in bone mineral density. And now that we’ve looked at this fracture data, we’re seeing a good correlation also then with the biomarker bone mineral density and the important decrease in fracture rate. The way we’re looking at fracture rate here and with discussion with the FDA and other regulatory agencies is that fracture rate on an annualized basis.
With this newest data release, what we’re looking for is a meaningful, important change in fracture rate with a reduction in the annual fracture rate for patients treated for at least six months, a reduction of 67%. The annualized fracture rate coming to this study was 0.72. Just under one fracture, four patients on an annualized basis. With this data, this annualized fracture date comes all the way down to zero. Twenty out of 24 of these patients have had no radiographically confirmed fracture since starting treatment with setrusumab, and the other four have. That’s what, on average with a median, really brings the annualized fracture rate down to zero.
To learn more about osteogenesis imperfecta, and other rare bone disorders, visit checkrare.com/diseases/musculoskeletal-diseases/