Ultragenyx and Mereo reported that two Phase III programs of the monoclonal antibody setrusumab missed primary endpoints, triggering steep market reactions and strategic reassessments. The failures, disclosed in company releases and market reports, leave the partners without a pivotal late-stage readout and force both firms to evaluate next steps for the osteogenesis imperfecta program. Markets reacted sharply: Mereo shares plunged into penny-stock territory and Ultragenyx stock tumbled, reflecting investor disappointment. Both companies noted some secondary endpoint activity, but neither achieved statistical significance on its primary endpoints—a requirement for regulatory approval and commercial launch. Clinical teams are now dissecting subgroup and secondary data to determine whether any populations or biomarker-defined cohorts justify continued development. The outcomes raise questions about target validation and endpoint selection in rare-disease bone programs, and will likely influence investor appetite for similar monoclonal antibodies. Regulatory and commercial implications are immediate: a late-stage failure in a high-cost development program typically forces cost cuts, partnership renegotiations, and potential pipeline reprioritization for small and mid-cap biotechs.