AstraZeneca reports Phase III results for efzimfotase alfa in hypophosphatasia, showing strong paediatric efficacy and encouraging adult subgroup benefits.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Alexion AstraZeneca Rare Disease has reported positive results from its global Phase III programme evaluating efzimfotase alfa (ALXN1850), an investigational enzyme replacement therapy for hypophosphatasia (HPP), a rare inherited metabolic disorder affecting bone mineralisation and muscle function.
The clinical programme included three Phase III trials MULBERRY, CHESTNUT and HICKORY enrolling 196 patients across 22 countries, spanning paediatric, adolescent and adult populations with both paediatric- and adult-onset disease.
Efzimfotase alfa is designed as a next-generation alternative to Strensiq, with lower injection volume and less frequent dosing, aiming to address treatment burden and expand access across broader patient groups.
Marc Dunoyer, CEO, Alexion AstraZeneca Rare Disease, highlighted that the Phase III programme is the first to include both paediatric- and adult-onset HPP, capturing diverse disease manifestations. He added that the overall data support efzimfotase alfa’s potential to transform treatment for this rare disease.
In the MULBERRY trial (NCT06079359), efzimfotase alfa met its primary endpoint, demonstrating statistically significant and clinically meaningful improvements in bone health versus placebo at week 25, measured by Radiographic Global Impression of Change (RGI-C) score. Key secondary endpoints, including rickets severity (RSS), physical function and motor proficiency, also improved.
The CHESTNUT trial (NCT06079372) further showed that switching from Strensiq to efzimfotase alfa maintained treatment benefits, with favourable safety and tolerability in paediatric patients.
In the HICKORY trial (NCT06079281), efzimfotase alfa did not achieve statistical significance in the primary endpoint (6-minute walk test) in the overall adolescent and adult population, largely due to unexpectedly strong placebo performance.
However, the therapy demonstrated nominally significant improvements in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and in predefined subgroups of patients with paediatric-onset HPP, it showed clinically meaningful gains in mobility, physical function and pain reduction.
Findings from the ongoing open-label extension of the HICKORY trial showed continued improvements through week 48, including in patients who switched from placebo.
Across all three trials, efzimfotase alfa was well tolerated with an acceptable safety profile.
Eric Rush, Lead Investigator (MULBERRY), emphasised that the results demonstrate potential to address underlying disease biology and improve skeletal and functional outcomes. He noted the therapy could redefine HPP care with a convenient, biweekly self-administered option.
Kathryn Dahir, Lead Investigator (HICKORY), stated that the trial highlights disease heterogeneity and the importance of assessing multiple clinically meaningful endpoints across populations. She added that improvements in mobility, function, pain and fatigue support meaningful patient benefit.
Alexion plans to present these data at upcoming medical meetings and engage with global regulatory authorities, positioning efzimfotase alfa as a potential new treatment option across a wider spectrum of HPP patients.
Hypophosphatasia is caused by deficient alkaline phosphatase activity, leading to defective bone mineralisation, muscle weakness, fatigue and pain. The disease affects all age groups and remains underdiagnosed, with significant unmet need despite existing therapies.
References
Efzimfotase alfa demonstrated positive results from global Phase III clinical programme in hypophosphatasia, 31 March 2026, Efzimfotase alfa demonstrated positive results from global Phase III clinical programme in hypophosphatasia
About the Writer
Nikita Jha BPharm is a pharmacy graduate with expertise in clinical research, pharmacovigilance, and medical writing. In her words, she is passionate about translating complex scientific data into clear, accurate healthcare communications that advance drug safety and patient care.