Four years after betting up to $304 million on a drug for a rare genetic bone disorder, Ultragenyx and its partner Mereo BioPharma reported positive data in a Phase 2/3 trial.
The two companies are developing the monoclonal antibody setrusumab for osteogenesis imperfecta, which can cause brittle bones that break easily. In the Phase 2 portion of the Orbit trial, 24 patients saw their median annualized rate of fractures reduced by 67% after a mean treatment duration period of 16 months (p=0.0014). In the two years before treatment, these patients had radiologically confirmed fractures across at an annualized rate of 0.72, and it dropped to 0.00, according to Ultragenyx and Mereo.
The patients, between 5 years and 25 years old, were randomized to receive setrusumab at one of two doses as part of the companies’ plan to pick the best dosing strategy for the Phase 3 part of the study. All patients were treated for at least 14 months, and more detailed results will be shared in the future, the companies said.
The Phase 3 portion has enrolled another 158 patients who are randomized to get either setrusumab or a placebo, with the same primary endpoint of annualized clinical fracture rate and primary completion date slated for March 2025.
Mereo and Ultragenyx first paired up on the drug in 2020, with the latter paying $50 million upfront and promising another $254 million in milestones. As part of the deal, Ultragenyx took over developing the drug and commercializing it everywhere except for Europe. Mereo originally nabbed the drug from Novartis in 2015.
“The anti-sclerostin antibody appears effective even after a year and remarkably, patients continue to make measurable gains, suggesting we will see an ongoing response over the long term,” Gary Gottesman, professor of pediatrics and medicine at Washington University School of Medicine, said in a statement.
The drug also showed “ongoing and meaningful improvements” in lumbar spine bone mineral density after 12 months of treatment, with an increase of 22%, earning a p<0.0001. That’s an improvement from previously reported six-month data, which showed an increase of 14%.
As for safety, there were no treatment-related serious adverse events, with the most common adverse events being infusion-related as well as headaches.
The companies also have a separate Phase 3 study dubbed Cosmic, which is fully enrolled, to investigate the drug in patients 2 years old to younger than 7 years.