Two Phase III readouts of setrusumab for brittle‑bone disease missed primary endpoints, sending Ultragenyx and partner Mereo BioPharma into sharp stock declines. The programs, tested in separate Orbit and Cosmic Phase III trials, failed to meet their predefined efficacy targets despite achieving some secondary measures. Investors reacted swiftly: Mereo’s shares plunged sharply and Ultragenyx’s stock fell as market participants recalibrated the companies’ rare‑disease portfolios and revenue projections. Management teams indicated they will scrutinize the datasets to determine next steps, including potential program wind‑downs or alternative development paths. The failures underscore the risk in late‑stage rare‑disease trials and will prompt re‑evaluation by partners, payers and clinical investigators of setrusumab’s therapeutic hypothesis and future development options.