Mereo BioPharma and Ultragenyx Partner to Develop Setrusumab for Rare Bone Disease

Rare Daily Staff

Mereo BioPharma and Ultragenyx Pharmaceutical have entered into a license and collaboration agreement to develop and commercialize setrusumab for the treatment of osteogenesis imperfect, a rare bone disease.

Under their agreement, Mereo will receive $50 million upfront and is eligible for up to $254 million in milestone-based payments. Ultragenyx will lead and fund development of setrusumab to approval. Mereo retains commercial rights in Europe and Ultragenyx will commercialize it in the United States and the rest of the world.

Osteogenesis Imperfecta (OI) is a rare genetic disorder that is characterized by fragile bones and reduced bone mass resulting in bones that break easily, loose joints, and weakened teeth. In addition, people with OI often suffer muscle weakness, early hearing loss, fatigue, curved bones, scoliosis, respiratory problems, and short stature, leading to significant effects on overall health and quality of life. The majority of cases of OI are caused by a dominant mutation in a gene coding for type I collagen, a key component of healthy bone. Current treatment of OI is supportive, focusing on minimizing fractures and maximizing mobility, but to date, there are no approved treatments.

Setrusumab is a fully humanized monoclonal antibody that inhibits sclerostin, a protein that inhibits the activity of bone-forming cells. Data from a phase 2b study of setrusumab demonstrated a dose-dependent increase in bone formation, density, and strength in adults with OI. Setrusumab recently received Rare Pediatric Disease designation from the U.S. Food and Drug Administration, and was accepted into the European Medicines Agency’s Priority Medicines program (PRIME).

“Following the positive data from our phase 2b ASTEROID study, we set out to find the right partner and we believe that Ultragenyx, with its proven track record of successfully developing and commercializing novel therapies for rare diseases, is ideally positioned to support the further advancement of our innovative therapeutic candidate,” said Denise Scots-Knight, CEO of Mereo.

The companies will expand and initially prioritize the development of setrusumab for pediatric patients with OI. Development plans are being finalized for a pediatric phase 2/3 study that first focuses on determining the optimal dose based on increases in collagen production using serum P1NP levels and an acceptable safety profile. Following determination of the dose, the study is intended to adapt into a pivotal phase 3 stage, evaluating fracture reduction over an estimated 15 to 24 months as the primary endpoint pending regulatory review. The pediatric phase 2/3 study is expected to start in 2021. A separate pivotal study is also being planned for adults with OI.

Under the terms of the collaboration, Ultragenyx will lead future global development of setrusumab in both pediatric and adult patients. Ultragenyx will make an upfront payment of $50 million to Mereo and will fund global development of the program until approval, and has agreed to pay a total of up to $254 million upon achievement of certain clinical, regulatory, and commercial milestones. Ultragenyx will pay tiered double-digit percentage royalties to Mereo on net sales outside of Europe, and Mereo will pay a fixed double-digit percentage royalty to Ultragenyx on net sales in Europe. Under the terms of its 2015 agreement with Novartis, Mereo will pay Novartis a percentage of proceeds, subject to certain deductions, with Mereo receiving a substantial majority of the payments from Ultragenyx.

The deal builds on Ultragenyx’s existing bone franchise. “Setrusumab is a great complement to Ultragenyx’s product portfolio and enables us to leverage the broad expertise and infrastructure we have established in metabolic bone diseases with Crysvita,” said Emil Kakkis, president and CEO of Ultragenyx. “Most importantly, setrusumab is a promising option for patients with osteogenesis imperfecta, which is one of the most common genetic bone diseases associated with frequent bone fractures.”

Photo: Emil Kakkis, president and CEO of Ultragenyx