Ultragenyx Announces First Patient Dosed in Pivotal Phase 2/3 Clinical Study for the Treatment of Osteogenesis Imperfecta

Ultragenyx Pharmaceutical Inc. recently announced the first patient has been dosed in a clinical study for the treatment of Osteogenesis Imperfecta (OI) in patients ages 5 to <26 years of age. The pivotal Orbit study is a seamless Phase 2/3 study of setrusumab (UX143), an investigational anti-sclerostin fully human monoclonal antibody in development for the treatment of OI in children and adults with OI sub-types I, III and IV. Ultragenyx is leading the clinical development of setrusumab as part of a collaboration and license agreement with Mereo BioPharma Group plc (MREO), a clinical-stage biopharmaceutical company focused on oncology and rare diseases.

“The Orbit study builds on the findings of the 12-month Phase 2b ASTEROID study, which demonstrated that treatment with setrusumab resulted in a clear, dose-dependent and statistically significant effect on bone formation and bone density at multiple anatomical sites among adult participants with OI,” said Camille Bedrosian, MD, Chief Medical Officer at Ultragenyx. “The Orbit Phase 2/3 study is designed to study fracture risk reduction in a younger population, where the risk of fracture is higher and where we can potentially have the greatest impact on their future health.”

Tracy Hart, CEO of the Osteogenesis Imperfecta Foundation, added “The OI Foundation is excited about the potential for new treatments for our community and are encouraged that they will potentially have an impact on the overall quality of life for our community.”

Ultragenyx is planning additional studies for setrusumab, including an open-label, randomized Phase 3 study in patients aged 2 to <5 years evaluating setrusumab versus bisphosphonates for the treatment of OI over a period of 12 to 24 months that is anticipated to start in the second half of 2022. The company also plans to continue to study setrusumab in adult patients over the age of 25 with OI.

The global, seamless Phase 2/3 Orbit study will evaluate the effect of setrusumab versus placebo on fracture rate in patients aged 5 to <26 years with OI sub-types I, III, and IV. In the Phase 2 portion, 36 patients will be randomized 1:1:1 to receive setrusumab at one of two doses or placebo to determine the optimal dosing strategy for Phase 3. The Phase 3 dosing strategy will be developed based on initial Phase 2 safety, pharmacokinetic, and bone biomarker data.

The pivotal Phase 3 portion of the study will include approximately 195 participants, randomized 2:1 to receive setrusumab or placebo, with a primary endpoint of fracture rate reduction. All participants will transition to an extension period and receive open-label setrusumab after the Phase 3 primary analysis is complete, or once a participant has completed 24 months in the double-blind period, whichever is sooner. Further details can be referenced here: https://clinicaltrials.gov/ct2/show/NCT05125809

Osteogenesis Imperfecta (OI) includes a group of genetic disorders impacting bone metabolism. Approximately 85% to 90% of OI cases are caused by mutations in the COL1A1 or COL1A2 genes, leading to either reduced or abnormal collagen and changes in bone metabolism. The collagen mutations in OI can result in increased bone brittleness, which contributes to a high rate of fractures, including at atypical sites. Patients with OI also exhibit increased bone resorption (breakdown of old bone) and inadequate production of new bone, which leads to decreased bone mass, bone fragility and weakness. OI can also lead to bone deformities including abnormal spine curvature, pain, decreased mobility, and short stature. No treatments are approved for OI, which affects approximately 60,000 people in the developed world.

Setrusumab is a fully human monoclonal antibody that inhibits sclerostin, a protein that acts on a key bone-signaling pathway that inhibits the activity of bone-forming cells. The goal of blocking inhibitory effects of sclerostin is to increase new bone formation, bone mineral density, and bone strength. Sclerostin inhibition also reduces excessive bone resorption, further enhancing its impact on bone density. In various mouse models of OI, the use of anti-sclerostin antibodies was shown to stimulate bone formation, improve bone mass and density, and reduce bone fragility as reflected in increased long bone strength and reduced the number of fractures.

Mereo BioPharma’s Phase 2b study (ASTEROID) treatment phase of the dose-finding study of setrusumab for the treatment of OI in 112 adults was concluded in 2019. The ASTEROID study demonstrated treatment with setrusumab resulted in a clear, dose-dependent and statistically significant effect on bone formation and bone density at multiple anatomical sites among adult participants with OI. Off-treatment results were followed.

Ultragenyx and Mereo BioPharma are collaborating on the development of setrusumab globally based on the collaboration and license agreement between the parties. The companies are planning a comprehensive late-stage program to continue development of setrusumab in pediatric and young adult patients across OI sub-types I, III and IV.

Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease. The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency. For more information, visit www.ultragenyx.com.

For more information on Mereo BioPharma, please visit www.mereobiopharma.com.