Alexion, AstraZeneca Rare Disease, has reported positive results from its global Phase III clinical programme evaluating efzimfotase alfa (ALXN1850) in patients with hypophosphatasia (HPP), a rare inherited metabolic disorder. The programme, spanning three trials—MULBERRY, CHESTNUT, and HICKORY—enrolled 196 patients across 22 countries, including children, adolescents, and adults.

Efzimfotase alfa is an investigational enzyme replacement therapy designed to address key treatment gaps in HPP by offering lower injection volumes and less frequent dosing compared to existing therapies.

In the MULBERRY trial, conducted in treatment-naïve paediatric patients, efzimfotase alfa met its primary endpoint, demonstrating statistically significant and clinically meaningful improvements in bone health versus placebo. Additional benefits were observed in physical function and motor proficiency measures.

The CHESTNUT trial further supported its profile, showing that patients switching from standard therapy maintained bone health improvements, while demonstrating favourable safety and tolerability.

In the HICKORY trial involving adolescents and adults, the therapy showed numerical improvement in mobility, although it did not meet statistical significance for the primary endpoint due to strong placebo performance. However, meaningful improvements were observed in fatigue, physical function, and pain, particularly in patients with paediatric-onset HPP.

Across all studies, efzimfotase alfa demonstrated a consistent and acceptable safety profile. Ongoing extension studies indicate continued clinical benefits over longer treatment durations.

HPP is a rare, progressive disorder caused by deficient alkaline phosphatase enzyme activity, leading to impaired bone mineralisation, muscle weakness, and chronic pain. With limited treatment options currently available, there remains a significant unmet need for effective therapies across diverse patient populations.

For pharma manufacturing, these results highlight growing innovation in enzyme replacement therapies and the need for scalable production of advanced biologics targeting rare diseases. AstraZeneca continues to expand its rare disease pipeline, focusing on precision-driven treatments to improve outcomes for patients with high unmet medical needs.