Today Mereo BioPharma and its partner Ultragenyx announced that their phase 2/3 ORBIT study, which is using setrusumab for the treatment of patients with osteogenesis imperfecta (OI) is pressing on towards final analysis by the end of this year, 2025. Typically this would be highly good news for such companies; however, the hope was that the results would be good enough that this trial could be stopped early due to strong efficacy. For now, this is just a minor bump in the grand scheme of things. While it would have been nice if it had stopped the study early due to overwhelming efficacy, it is not the end of this program at all.
The reason why is because the company is still moving forward with this phase 2/3 ORBIT study to completion. Plus, it is also in the process of evaluating the use of this drug in the phase 3 COSMIC study, which is also expected to have data by year-end. There are a few differences with this study indeed. The ORBIT trial is focused on targeting patients with OI who are between the ages of 5 and 25, whereas the other COSMIC trial is treating patients ages 2 to < 7 years of age. In addition, the former is testing setrusumab compared to that of placebo, while the latter is testing the drug versus standard of care (SOC) intravenous (IV) bisphosphonates (IV-BP) treatment.
Osteogenesis Imperfecta is a genetic disorder of bone metabolism. What occurs is that defective genes affect how collagen comes together to keep bones intact. With this process being affected, bones are weak and frail, and it leads these patients to have a lot of fractures in their bones. That’s not all; these patients also have trouble with new bone formation as well. Setrusumab is a fully human monoclonal antibody that inhibits sclerostin, which is a negative regulator of the formation of bones. The point here is that this doesn’t allow bones to strengthen, leading to frailty. The drug from Mereo and partner Ultragenyx is designed to block sclerostin and increase bone formation. Plus, to also increase bone mineral density so that these patients don’t experience a lot of fractures.
It remains to be seen what happens with the ongoing late-stage ORBIT and COSMIC studies, but the mechanism of action (MOA) of the new formation of bones the drug allows for was shown with phase 2 portion data released from the phase 2/3 ORBIT trial. From this, it was revealed that 24 OI patients treated over a 16-month period achieved a mean annualized fracture reduction rate of 67%. Another way of looking at this is that in the 2-year period before these patients were treated, the radiologically confirmed fracture rate for these patients was 0.72, but after treatment, this rate was reduced to 0.00.
As I noted above, a major problem for these OI patients is lack of bone mineral density. With that being said, the patients from this released data showed to have achieved an average increase in bone mineral density from baseline of 22%. This measure ended up being achieved in a statistically significant manner with a p-value of p<0.0001. The company has a significant amount of cash to reach these expected catalysts that are rapidly approaching towards the end of this year. As of the end of March 31, 2025, it had cash of $62.5 million. This is expected to be enough to help it fund its operations into 2027.
Mereo believes that the use of setrusumab for OI and the serine protease inhibitor alvelestat for the treatment of patients with Alpha-1 Antitrypsin Deficiency-associated Lung Disease (AATD-LD) could each garner >$1 billion of market opportunities. Lastly, there are currently no FDA or European Medicines Agency (EMA)-approved therapies to treat these patients with OI. If this company can achieve positive results in both of the ongoing late-stage studies, along with obtaining marketing approvals of this drug for these patients in both of these territories, then it will have the entire market all to itself.