AstraZeneca (LSE/STO/NYSE: AZN) reported detailed results from the Phase III HICKORY trial of efzimfotase alfa (ALXN1850) in treatment-naïve adolescents and adults with hypophosphatasia (HPP), showing a least squares mean treatment difference of 17.05 meters versus placebo in the Six-Minute Walk Test (6MWT) at Week 25 (p=0.1675), failing to reach statistical significance. The primary endpoint miss was previously disclosed in March 2026, while the latest data, presented at the American Society for Bone and Mineral Research 2026 Annual Meeting, provide additional detail on differences between patient subgroups.
The 124-patient trial compared efzimfotase alfa (n=84) with placebo (n=40). AstraZeneca attributed the overall endpoint failure largely to better-than-expected placebo performance in patients with adult-onset HPP, where the 6MWT treatment difference was -2.70 meters (nominal p=0.8764). In contrast, the prespecified pediatric-onset subgroup (n=60) showed a 35.6-meter benefit (nominal p=0.0386). The key secondary FACIT-Fatigue endpoint also showed a nominally significant improvement (least squares mean difference 5.74; nominal p=0.0016), while mobility and pain endpoints numerically favored efzimfotase alfa without reaching nominal statistical significance. The secondary and subgroup p-values were not adjusted for multiplicity.
AstraZeneca said efzimfotase alfa was generally well tolerated, with no new safety signals identified across the Phase III program. The company did not provide a separate detailed adverse event breakdown for HICKORY in the latest announcement.
The US FDA granted Priority Review to efzimfotase alfa in September 2026 for patients with HPP aged two years and older, based on the three-trial Phase III program comprising HICKORY, MULBERRY, and CHESTNUT. The companion MULBERRY trial demonstrated statistically significant improvements in bone health in treatment-naïve pediatric patients, while CHESTNUT evaluated patients previously treated with Strensiq (asfotase alfa). A US FDA decision on efzimfotase alfa is expected in H1 2027.