Alexion, AstraZeneca Rare Disease, has announced positive results from its Phase 3 clinical programme evaluating investigational enzyme replacement therapy efzimfotase alfa (ALXN1850) for the treatment of hypophosphatasia (HPP), a rare inherited metabolic bone disorder. The late-breaking findings from the MULBERRY trial were presented during the 12th International Conference on Children's Bone Health (ICCBH) in Montreal.

The global Phase 3 MULBERRY trial met its primary endpoint, with treatment-naïve children aged between two and under 12 years receiving efzimfotase alfa demonstrating a statistically significant and clinically meaningful improvement in bone health compared with placebo. Bone health was assessed using the Radiographic Global Impression of Change (RGI-C) score at Week 25.

The study also achieved its key secondary endpoint, with patients showing significant improvement in the Rickets Severity Score (RSS). In addition, children treated with efzimfotase alfa experienced improvements in physical function and quality of life, including better performance in the Paediatric Outcomes Data Collection Instrument (PODCI) Global Function score and clinically meaningful gains in the Six-Minute Walk Test (6MWT).

Separately, results from the Phase 3 CHESTNUT trial showed that children who switched from Strensiq (asfotase alfa) to efzimfotase alfa maintained bone health while demonstrating a safety profile comparable to those who continued on Strensiq. The therapy was generally well tolerated, with similar rates of treatment-emergent adverse events between both groups.

Alexion also reported that pooled data from the MULBERRY and HICKORY studies demonstrated a favourable safety profile for efzimfotase alfa, with approximately five times fewer injection-site reactions than those reported with Strensiq during the first 24 weeks of treatment. Patients treated with efzimfotase alfa also experienced a high proportion of injection-site reaction-free days during long-term follow-up.

The ongoing HICKORY Phase 3 study is evaluating efzimfotase alfa in adolescents and adults with hypophosphatasia, with full results expected to be presented at a future medical meeting.

Commenting on the findings, investigators noted that hypophosphatasia can lead to severe and progressive skeletal, neurological and functional complications that significantly affect children's physical development and quality of life. They said the trial results represent an important advancement in addressing the underlying enzyme deficiency responsible for the disease.

Alexion stated that efzimfotase alfa is being developed as a next-generation enzyme replacement therapy administered once every two weeks through subcutaneous injection. The therapy is designed to replace deficient alkaline phosphatase enzyme activity, the root cause of hypophosphatasia, while offering improved convenience and tolerability.

Hypophosphatasia is a rare, chronic genetic disorder caused by deficient alkaline phosphatase activity, leading to impaired bone mineralisation, muscle weakness, pain and other debilitating complications. The disease affects both children and adults, with an estimated 11,500 diagnosed patients across major global markets.