AstraZeneca Says Efzimfotase Alfa (ALXN1850) Phase 3 Program For Hypophosphatasia Demonstrated Positive Results

The efzimfotase alfa (ALXN1850) Phase III clinical programme, designed to study a broad hypophosphatasia (HPP) patient population, demonstrated positive results. The global clinical programme, which included two randomised, placebo-controlled trials and one randomised, open-label, active-controlled paediatric switch trial, enrolled 196 patients spanning children, adolescents and adults with either paediatric-onset or adult-onset HPP across 22 countries.Addressing unmet needs for people living with HPPEfzimfotase alfa is an investigational enzyme replacement therapy designed to offer lower injection volume, less frequent dosing over Strensiq (asfotase alfa) and close critical gaps in care within the broader HPP patient population.Paediatric clinical trialsThe MULBERRY Phase III trial in children (2 to Strensiq, showed that efzimfotase alfa met its primary endpoint. Results demonstrated a statistically significant and clinically meaningful improvement in bone health from baseline compared to placebo, as measured by Radiographic Global Impression of Change (RGI-C) Score at week 25. In addition, statistically significant improvement was observed in the key secondary endpoint of change from baseline in Rickets Severity Score (RSS) at week 25. Additional secondary endpoints measuring physical function (Six-Minute Walk Test) and motor proficiency (Paediatric Outcomes Data Collection Instrument or PODCI) further supported the overall clinical benefit of efzimfotase alfa in the paediatric population.Positive high-level results from the CHESTNUT Phase III trial showed that efzimfotase alfa was well-tolerated and demonstrated a favourable safety profile in paediatric patients (2 to Strensiq and maintained the treatment benefit of Strensiq on bone health at week 25, as measured by secondary endpoints RGI-C and RSS.Adolescent and adult clinical trialIn the HICKORY Phase III trial, efzimfotase alfa showed numerical improvement but did not achieve statistical significance in the primary endpoint of Six-Minute Walk Test (6MWT) in adolescents and adults (12 years of age and older) with HPP who have not been previously treated with Strensiq, compared to placebo at week 25. This was largely due to better-than-expected results observed in the adult-onset HPP placebo group. However, treatment with efzimfotase alfa demonstrated nominally significant improvements in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) in the overall study population.In a combination of prespecified subgroups of adolescents and adults with paediatric-onset HPP, efzimfotase alfa showed nominally statistically significant and clinically meaningful benefits in mobility, as measured by 6MWT, as well as key secondary endpoints measuring physical function and pain reduction, compared to placebo.Initial findings from the ongoing, long-term, open-label extension of the HICKORY trial show continued improvement in the primary and key secondary endpoints at week 48. Participants who switched from placebo to efzimfotase alfa after the randomised period also showed clinically meaningful improvements across multiple efficacy outcomes after 24 weeks of treatment.Efzimfotase alfa was well-tolerated and had an acceptable safety profile across the MULBERRY, CHESTNUT and HICKORY clinical trials.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."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."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."These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.