Ultragenyx-Mereo's brittle bone drug maintains fracture reduction in midphase trial

Ultragenyx and Mereo BioPharma have released promising new data regarding their drug candidate, setrusumab, which is being tested for its efficacy in reducing fracture rates in patients with osteogenesis imperfecta. This disease, often referred to as brittle bone disease, causes bones to fracture easily due to genetic defects.

The latest results come from the first segment of the phase 2/3 Orbit study, which included 24 patients. Prior to starting the trial, these patients had a median annualized fracture rate of 0.72 over the previous two years. After approximately nine months of treatment with setrusumab, the median annualized fracture rate fell to zero, a significant reduction that was first reported in October.

Now, after an average of 16 months on the drug, the partners have reported sustained outcomes. The fracture rate remains at zero, representing a 67% reduction compared to pre-trial data. This consistency builds on earlier findings, strengthening the case for setrusumab as a viable treatment for osteogenesis imperfecta. In comparison, current treatments like pamidronate and zoledronic acid show lower rates of fracture reduction.

This result aligns with the expectations set by Mereo BioPharma's CEO Denise Scots-Knight, who mentioned during a Jefferies event that the new data would likely be "at least comparable, if not better than" the previous results. Following this announcement, Mereo's stock price rose by more than 6% to $3.75 in premarket trading, while Ultragenyx's stock increased by 4% to over $43.

In addition to fracture rates, the study also provided updated information on bone mineral density (BMD). According to Scots-Knight, BMD is a critical indicator to monitor, as it can inform future maintenance dosing regimens. The lumbar spine BMD of patients increased by 22% from baseline after 12 months of treatment, showing no signs of plateauing. This continued growth is an improvement over the 14% increase reported after six months and suggests ongoing potential for further gains.

These encouraging results come as Ultragenyx and Mereo move toward the phase 3 portion of the trial. Ultragenyx has already completed enrollment for this phase, which includes participants aged 5 to 25 years, as well as another phase 3 study focusing on younger children. Speaking at a Goldman Sachs event, Ultragenyx CEO Emil Kakkis mentioned that an interim analysis is expected around the end of 2024. Kakkis expressed optimism about the trial's progress, suggesting that the trial might conclude earlier than anticipated, depending on the number of fractures observed.

"I think we'll end early, but I don't know for sure," Kakkis stated. "Based on the size of the trial, and the fracture reduction we're seeing, we should. But it highly depends on how many fractures are happening. That part is hard to predict."

In summary, the sustained reduction in fracture rates and the continued increase in bone mineral density provide substantial encouragement for Ultragenyx and Mereo BioPharma. These findings will be integral as they advance to the next phase of the trial, aiming to provide a new, effective treatment option for individuals suffering from osteogenesis imperfecta.