Astra Zeneca’s Efzimfotase Alfa Improves Bone Health in Hypophosphatasia Trial

Alexion, AstraZeneca Rare Disease, reported positive late-breaking Phase III results showing that efzimfotase alfa (ALXN1850) significantly improved bone health in children with hypophosphatasia (HPP) who had not previously received enzyme replacement therapy. Findings from the MULBERRY trial were presented during a late-breaking oral session at the 12th International Conference on Children’s Bone Health (ICCBH) in Montreal, Canada.

The results strengthen the clinical profile of efzimfotase alfa across the company’s Phase III HPP programme, which also includes the CHESTNUT and HICKORY studies evaluating treatment-experienced children and older patients.

Investigational enzyme replacement therapy for HPP

Hypophosphatasia is a rare inherited metabolic disorder caused by deficient alkaline phosphatase (ALP) activity, resulting in impaired bone mineralisation, muscle weakness, chronic pain, neurological symptoms, and progressive functional disability. Approximately 80% of diagnosed patients are adults, although severe disease often begins during childhood.

Efzimfotase alfa is an investigational enzyme replacement therapy administered as a subcutaneous injection once every two weeks to replace deficient ALP activity. If approved, it could offer a less burdensome alternative to Strensiq (asfotase alfa), which requires three to six injections each week.

 MULBERRY trial met primary and key secondary endpoints

The global Phase III MULBERRY trial (NCT06079359) enrolled 29 treatment-naïve children aged 2 to under 12 years with HPP. Patients were randomised to receive efzimfotase alfa or placebo for 24 weeks.

The study met its primary endpoint, with patients receiving efzimfotase alfa achieving a median Radiographic Global Impression of Change (RGI-C) score of 1.67 compared with 0 for placebo (95% CI 0.66-2.00; p=0.0003).

The therapy also significantly improved the Rickets Severity Score (RSS), showing a median change of -1.00 versus 0 with placebo (95% CI -2.00 to -0.33; p=0.0008).

Secondary analyses showed improvements in physical function and quality of life, including higher Paediatric Outcomes Data Collection Instrument (PODCI) Global Function scores and clinically meaningful gains in the Six-Minute Walk Test. Improvements were also observed across motor function and health-related quality-of-life measures.

Safety profile remained favourable across Phase III programme

The CHESTNUT Phase III study (NCT06079372) evaluated children who switched from long-term Strensiq therapy to efzimfotase alfa. Treatment-emergent adverse events occurred at similar rates in patients receiving efzimfotase alfa (90.5%) and those remaining on Strensiq (86.4%), while bone health remained stable after switching.

Across pooled data from the MULBERRY and HICKORY studies, efzimfotase alfa demonstrated a favourable tolerability profile. Injection-site reactions occurred at approximately one-fifth the annualised rate reported with Strensiq during its registrational programme, and patients experienced a median 98.8% injection-site reaction-free days during treatment.

Clinical programme continues

According to principal investigator Jill Simmons, MD, the findings demonstrate clinically meaningful improvements in skeletal health and physical function for children living with HPP during critical stages of development.

Alexion also highlighted that the Phase III programme represents the largest and most comprehensive clinical investigation conducted in HPP. The company expects full Phase III results from the HICKORY trial (NCT06079281) in adolescents and adults aged 12 years and older to be presented at an upcoming medical meeting, further defining the therapeutic potential of efzimfotase alfa across the broader HPP population.

Reference

Efzimfotase alfa demonstrated improvements in bone health in treatment-naïve paediatric patients with hypophosphatasia achieving median difference of 1.67 vs placebo in RGI-C Score at week 25 in MULBERRY Phase III trial