Partners Ultragenyx and Mereo BioPharma saw their stocks drop by 21% and 30%, respectively, after announcing that the Phase II/III study of their osteogenesis imperfecta candidate will proceed to final analysis, implying it did not show sufficiently strong results at an interim analysis.
A Phase II/III study of Ultragenyx and Mereo BioPharma’s investigational osteogenesis imperfecta therapy UX143 will proceed to its final analysis, suggesting the trial fell short of an efficacy bar that would have led the companies to end the trial ahead of schedule.
Writing to investors on Thursday morning, analysts at Wiliam Blair said the announcement implies that at the second interim analysis the trial, dubbed Orbit, “did not meet the minimal p-value threshold of p<0.01 to end the study early.”
The Orbit announcement came after markets closed on Wednesday. In premarket trading Thursday, Ultragenyx was down by 21% and Mereo by 30%.
To preserve the integrity of the study, the partners did not reveal specific efficacy data on Wednesday, only stating that the data monitoring committee for Orbit found that UX143 had an “acceptable” safety profile. The lack of information, according to William Blair, makes it “challenging to speculate why and by how much the second interim [analysis] did not achieve its threshold.”
Still, the analysts appeared to remain optimistic about Orbit, writing that they “still believe there is a high likelihood that the final analysis in the fourth quarter will be positive” given a lower bar for statistical significance at that point, and a longer patient follow-up. “We see the market reaction . . . as severely overdone,” they added.
Afflicting 1 in 15,000 to 20,000 births, osteogenesis imperfecta (OI) is a rare genetic disorder that leads to severely brittle bones; patients with this condition sustain broken bones easily, even from minimal impact.
According to Ultragenyx and Mereo, around 85% to 90% of OI cases are caused by mutations in the COL1A1 or COL1A2 genes, which under healthy conditions encode for crucial components of the structural molecule collagen. Alterations in these genes can lead to lower or dysfunctional collagen and changes in bone metabolism, giving rise to the hallmark symptoms of OI.
UX143, also known as setrusumab, is an investigational monoclonal antibody that targets and blocks sclerostin, a protein that suppresses the formation of bones. Ultragenyx teamed up with Mereo on the drug’s development in 2020, paying $50 million upfront and up to $254 million more in milestones. The partners are proposing to leverage UX143’s mechanism of action to boost the formation of bone and normalize bone mass, while also strengthening bones against fractures.
Phase IIb data released in November 2019 showed that various doses of UX143 could improve total volumetric bone mineral density by 4.1% to 4.5% over 12 months of treatment.
Ultragenyx and Mereo are also running the pivotal Phase III Cosmic trial, an open-label, randomized and active-controlled study testing the antibody in 69 patients aged 2 through 6 years. Results from Orbit and Cosmic are expected “around the end of this year,” Ultragenyx CEO Emil Kakkis said in a statement on Wednesday.
