AstraZeneca’s Efzimfotase Alfa Demonstrates Positive Phase 3 Results In Hypophosphatasia Across Age Groups

The Phase III clinical programme for efzimfotase alfa (ALXN1850), an investigational enzyme replacement therapy for hypophosphatasia (HPP), has reported positive results across a broad patient population. The global programme included 196 patients across children, adolescents, and adults from 22 countries, evaluated through two randomised, placebo-controlled trials and one open-label, active-controlled paediatric switch study.

Eric Rush, MD, Clinical Geneticist, Children’s Mercy Hospital Kansas, Professor of Paediatrics, University of Missouri-Kansas City School of Medicine and lead principal investigator in the MULBERRY trial, said: “The results from the global MULBERRY clinical trial demonstrate efzimfotase alfa’s potential to address the underlying pathophysiology of HPP and to prevent and reverse the substantial skeletal and functional impacts of this lifelong rare disease. I am encouraged by these results and the potential for this innovative, investigational therapy to redefine care in HPP with a convenient self-administered option taken every two weeks.”

In paediatric patients, the MULBERRY Phase III trial met its primary endpoint, demonstrating significant improvements in bone health compared to placebo, as measured by RGI-C scores at week 25. Additional benefits were observed in rickets severity, physical function, and motor skills. The CHESTNUT trial further confirmed that efzimfotase alfa was well tolerated in children switching from Strensiq (asfotase alfa), maintaining bone health benefits with a favourable safety profile.

Kathryn Dahir, MD, Director of the Programme for Metabolic Bone Disorders at Vanderbilt Health and Associate Director for Clinical Research Translation, Professor in the Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism and lead investigator in the HICKORY trial, said: “Findings from the broad HICKORY registrational trial, the first to include patients with adult-onset disease, highlight the heterogeneity of the disease and the value of assessing a range of clinically meaningful endpoints across diverse patient populations. The results indicate a clinically relevant impact on mobility, physical function, pain and fatigue, demonstrating the potential for efzimfotase alfa to improve outcomes for patients living with this disease.”

In adolescents and adults, results from the HICKORY trial showed numerical improvements in mobility but did not reach statistical significance for the primary endpoint, partly due to unexpectedly strong placebo responses. However, the therapy demonstrated improvements in fatigue and showed clinically meaningful benefits in specific subgroups, particularly those with paediatric-onset HPP.

Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease, said: “The efzimfotase alfa clinical programme, comprised of three global Phase III trials, was the first to include patients with both paediatric- and adult-onset HPP with heterogeneous manifestations beyond bone. We are encouraged by the improvements observed across this patient population who exhibit a wide range of severity and clinical characteristics. Collectively, these results support the potential for efzimfotase alfa to transform the treatment paradigm for people living with this rare disease.”

Overall, efzimfotase alfa showed a consistent safety profile across all trials, with ongoing extension data indicating sustained improvements over time. The therapy is being developed to address unmet needs in HPP by offering reduced injection volume and less frequent dosing compared to existing treatments.