Ultragenyx Gains Breakthrough Therapy Status for Setrusumab in Osteogenesis Imperfecta

On October 7, 2024, Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical firm dedicated to developing innovative treatments for rare and ultra-rare diseases, announced that the U.S. Food and Drug Administration (FDA) has awarded Breakthrough Therapy Designation to setrusumab (UX143). This designation is for the treatment of osteogenesis imperfecta (OI) Types I, III, and IV in patients aged two years and older to reduce fracture risk.

Dr. Eric Crombez, Chief Medical Officer at Ultragenyx, highlighted the significance of this designation, stating, "The FDA’s recognition of setrusumab as a Breakthrough Therapy underscores the severe nature of osteogenesis imperfecta and its profound impact on affected individuals and their families. The designation also acknowledges the substantial clinical benefits noted in the Phase 2 Orbit study and supports our efforts to swiftly deliver this investigational therapy to patients who currently lack approved treatment options."

The FDA’s decision was influenced by preliminary clinical evidence, including favorable 14-month outcomes from the Phase 2 Orbit study, which indicated a noticeable and significant reduction in fracture rates among patients. Additionally, the completed Phase 2b ASTEROID study contributed to the evidence. Breakthrough Therapy Designation seeks to expedite the development and review process for drugs aimed at treating serious or life-threatening conditions, particularly when early clinical data suggest that the drug could offer considerable improvement over existing treatments on clinically significant endpoints.

Setrusumab has previously been granted Orphan Drug Designation in both the United States and the European Union. It also received rare pediatric disease designation in the U.S. and has been accepted into the European Medicine Agency’s Priority Medicines program (PRIME).

Osteogenesis Imperfecta is a collection of genetic disorders that affect bone metabolism. Around 85% to 90% of OI cases are due to genetic mutations in the COL1A1 or COL1A2 genes, resulting in either deficient or abnormal collagen production, which subsequently disrupts bone metabolism. These collagen mutations cause increased bone brittleness, leading to a high fracture rate. Patients with OI suffer from inadequate new bone production and excessive bone resorption, causing reduced bone mineral density, bone fragility, and weakness. Additionally, OI can result in bone deformities, abnormal spine curvature, pain, reduced mobility, and short stature. Globally, no treatments have been approved for OI, which impacts approximately 60,000 people in commercially accessible regions.

Setrusumab is a fully human monoclonal antibody that inhibits sclerostin, a negative regulator of bone formation. By blocking sclerostin, setrusumab is expected to enhance new bone formation, bone mineral density, and bone strength in OI patients. In mouse models of OI, the use of anti-sclerostin antibodies has been shown to boost bone formation, restore bone mass to normal levels, and increase bone strength to normal levels according to fracture force tests.

In 2019, Mereo BioPharma completed the Phase 2b dose-finding study (ASTEROID) for setrusumab in 112 adult OI patients. This study demonstrated that setrusumab treatment had a clear, dose-dependent, and statistically significant impact on bone formation and density at various anatomical sites in adult OI participants.

Ultragenyx and Mereo BioPharma are collaborating globally on the development of setrusumab, based on their collaborative and license agreement. They have created a comprehensive late-stage development program to continue advancing setrusumab for pediatric and young adult patients across OI types I, III, and IV.

Ultragenyx is committed to delivering novel therapies to patients suffering from serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical needs and clear biological foundations, often where no approved therapies exist.

The company's leadership team is experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy focuses on time- and cost-efficient drug development, aiming to deliver safe and effective therapies to patients with urgency.