On December 29^th we learned from announcements from the companies Ultragenyx and Mereo Biopharma that the clinicals trials Orbit and Cosmic to failed to meet their main endpoint, which was reduced number of fractures in children with OI.

The Cosmic and Orbit trials

There are a lot of clinical trials investigating different therapies in OI these days. The two most central trials until now, have been the Cosmic and Orbit studies. These trials were carried out by the companies Mereo Biopharma and Ultragenyx and phase III was finalized in December 2025.

The Orbit study compared UX143 in children and young people with OI (between 5 and 26) with placebo. The study aimed to understand the potential reduction of fractures as well as other impacts such as bone density.

The Cosmic study compared UX143 in children from 2 to 7 against treatment with intravenous bisphosphonates. The study had reduction of fractures as the main endpoint, but also looked at other parameters such as bone density.

Bone density was improved, but fractures were not reduced

Even if fractures were not reduced, there were some positive effects in the Cosmic and Orbit trials. Both studies met their secondary endpoints of improvements in bone mineral density (BMD) when you compared to placebo and bisphosphonates. And this with a strong statistical significance. And there were no major side effects reported, which is also good news.

EMA & FDA – what happens after phase III if a drug trial is successful?

If a clinical trial shows promising results from a phase III, it means that the drug can be ready to apply for market approval by regulators like the European Medicines Agency (EMA) and the American counterpart FDA. The EMA/FDA evaluates risk/benefit and decides if a drug should be let into the market or not. The company then decides which countries they want to ask for national approval in. National agencies and payers then evaluate and decide whether the new drug should be approved and paid for on a national level. The process to evaluate cost/benefit is called Health Technology Assessment (HTA). From 2026 parts of this process happen on a European level.

What does these results mean for the companies?

After the press release, both Mereo and Ultragenyx have been in contact with the OIFE, discussing the results and what will happen next. Both companies are very clear on the fact that they are surprised and disappointed by the results and that this is not what they were expecting or hoping for. They are now working hard on further data analyses to understand if there are enough positive findings for it to make sense to move forward with the regulators (EMA and FDA).

What does it mean for the OI-community?

OIFE obviously share the disappointment that neither of the trials met their primary endpoint. We are hopeful that the further analysis around bone density and other factors will bring something positive. We will update the community as soon as we know more.

Were you part of the trial? 

Have you or your families been part of the trials – please contact your clinicians/local investigators if you have questions. Questions about the trial can also be asked to  OIstudyinfo@ultragenyx.com