Two late‑stage trials of setrusumab failed primary endpoints, sending shares of developers Mereo BioPharma and Ultragenyx tumbling and prompting strategic reassessments. The partners reported that neither the Orbit nor Cosmic Phase III studies met their primary efficacy measures in osteogenesis imperfecta, though some secondary endpoints were achieved. Markets reacted harshly: Mereo’s stock plunged and Ultragenyx shares fell sharply on the news, triggering immediate investor and management scrutiny. Both companies face decisions on whether to pursue additional analyses, regulatory discussions, or program terminations. The clinical setbacks underscore the execution risk of late‑stage rare‑disease programs and will likely affect investor appetite for similar bone disease assets.