The global Phase III clinical programme for efzimfotase alfa (ALXN1850) has delivered encouraging results in patients with hypophosphatasia (HPP), a rare, lifelong metabolic bone disorder. 

 

The programme, spanning 22 countries, enrolled 196 patients—including children, adolescents, and adults with both paediatric- and adult-onset HPP—through two randomized, placebo-controlled trials and one open-label paediatric switch trial.

 

Efzimfotase alfa is an investigational enzyme replacement therapy designed to reduce injection volume, allow less frequent dosing than Strensiq (asfotase alfa), and address unmet needs across the broad HPP patient population.

 

The MULBERRY Phase III trial, which studied children aged 2 to <12 years who were treatment-naïve to Strensiq, showed efzimfotase alfa met its primary endpoint. 

 

Patients experienced statistically significant and clinically meaningful improvements in bone health, measured by Radiographic Global Impression of Change (RGI-C) at week 25. Key secondary endpoints, including Rickets Severity Score (RSS), Six-Minute Walk Test, and motor proficiency (PODCI), also demonstrated significant improvements.

 

The CHESTNUT Phase III trial, examining children switching from Strensiq, confirmed the therapy’s favorable safety profile and maintained bone health benefits at week 25.

 

In the HICKORY Phase III trial, adolescents and adults (≥12 years) not previously treated with Strensiq showed numerical improvement in the Six-Minute Walk Test, though it did not reach statistical significance due to unexpectedly strong placebo results in the adult-onset group. 

 

However, efzimfotase alfa delivered nominally significant improvements in fatigue (FACIT-Fatigue) and, in subgroups of paediatric-onset HPP, demonstrated meaningful benefits in mobility, physical function, and pain reduction.

 

Long-term data from the ongoing open-label extension show continued improvements at week 48, with patients switching from placebo to efzimfotase alfa also showing clinically meaningful gains after 24 weeks. Across all trials—MULBERRY, CHESTNUT, and HICKORY—the therapy was well-tolerated with an acceptable safety profile.

 

Eric Rush, lead investigator of 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.”

 

Dr. Kathryn Dahir, lead investigator of the HICKORY trial, added: “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, CEO of Alexion, AstraZeneca Rare Disease, commented: “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.”