AstraZeneca’s experimental enzyme replacement therapy for hypophosphatasia posted mixed late-stage trial outcomes across three pivotal studies, according to reporting. The treatment, efzimfotase alfa, is aimed at a rare genetic condition that can cause soft and weak bones. The setback adds pressure to AstraZeneca’s rare-disease expansion plans, especially as enzyme-replacement competitors continue to mature and as regulators scrutinize efficacy consistency across late-stage datasets. For developers, the results also reinforce how even mechanism-consistent programs can face uneven efficacy signals when trial populations, endpoints, and comparators vary across late-stage studies.