Ultragenyx, Mereo Highlight Lasting Benefits of Brittle Bone Disease Drug

Ultragenyx and Mereo BioPharma have announced encouraging longer-term outcomes for their investigational anti-sclerostin antibody, setrusumab. This treatment has shown sustained reductions in fracture rates and improvements in bone mineral density (BMD) for patients with osteogenesis imperfecta (OI), a rare hereditary condition characterized by brittle bones. These results build on earlier six-month data which demonstrated a 67% decrease in the annualized rate of radiologically confirmed fractures among all 24 patients in the Phase II segment of the pivotal ORBIT trial, following at least six months of setrusumab treatment.

The new findings reveal that the benefits of setrusumab were maintained over at least 14 months of follow-up in OI patients. Additionally, setrusumab resulted in a mean 22% increase in lumbar spine BMD at the 12-month mark compared to baseline levels for all age groups in the study, which includes patients aged 5 to under 26 years. This improvement in BMD led to a substantial normalization in the Z-score, which saw an increase of +1.25, progressing from a +0.85 rise observed at six months.

"The clinically meaningful and continued enhancement in BMD implies that new and stronger bone is being formed, which has led to a notable reduction in fractures across different age groups and types of OI," stated Eric Crombez, chief medical officer at Ultragenyx.

No new safety concerns were observed with the longer-term use of setrusumab. There were no serious adverse events related to the treatment, and adverse events were "generally consistent" with those previously reported in the Phase IIb ASTEROID study, which included 112 adults with OI. Detailed data covering the 14-month period will be presented at a future scientific meeting.

The Phase III portion of the ORBIT study is currently ongoing, with 158 additional patients aged 5 to 25 years enrolled and randomized to receive either setrusumab or a placebo. The primary endpoint of this study is the annualized clinical fracture rate, with primary completion expected early next year. Simultaneously, the open-label Phase III COSMIC study is evaluating 69 children aged 2 to 7 years, randomizing them to setrusumab or intravenous bisphosphonate therapy, with a focus on the reduction in total fracture rate.

Enthusiasm for setrusumab is growing. Goldman Sachs analyst Salveen Richter recently expressed confidence in the drug, citing positive feedback from key opinion leaders regarding the Phase II data. She emphasized the potential of setrusumab to not only improve bone formation and strength but also reduce fractures through its sclerostin inhibition mechanism, a key differentiator from standard-of-care bisphosphonates.

Ultragenyx entered a collaboration and licensing agreement with Mereo in 2020 to strengthen its existing bone franchise, which includes Crysvita (burosumab-twza) for X-linked hypophosphatemia and tumor-induced osteomalacia. As part of the deal, Mereo received $50 million upfront and is eligible for milestones up to $254 million.