Efzimfotase alfa highlights meaningful bone health improvements in treatment-naïve paediatric patients with hypophosphatasia, achieving a median difference of 1.67 versus placebo in RGI-C score at week 25 in the MULBERRY Phase III trial

Findings from the MULBERRY Phase III trial showed that efzimfotase alfa, which is an investigational enzyme replacement therapy, produced a statistically significant and clinically meaningful gain in bone health in children aged 2 to under 12 with hypophosphatasia who had not previously received Strensiq. Improvement was measured using the Radiographic Global Impression of Change score at week 25 against placebo.

These late-breaking results were shared during an oral session at the 12th International Conference on Children’s Bone Health in Montreal, Canada.

The trial also cleared its key secondary endpoint in bone health as captured by the Rickets Severity Score, recording a statistically significant improvement at week 25. The efzimfotase alfa group posted an observed median of minus 1.00 against 0 in the placebo arm, with a median difference of minus 1.00 (p=0.0008).

Beyond bone health, efzimfotase alfa delivered improvements across secondary endpoints covering physical function and quality of life at week 25. A nominally significant median difference of 9.0 was recorded in the Paediatric Outcomes Data Collection Instrument Global Function normative score, alongside a clinically meaningful improvement in the Six-Minute Walk Test, where participants on efzimfotase alfa walked a median of 34.5 metres further than those on placebo.

In the CHESTNUT trial, children aged 2 to under 12 who switched to efzimfotase alfa from Strensiq showed a comparable incidence of treatment-emergent adverse events at week 25 to those who remained on Strensiq, at 90.5% and 86.4% respectively, alongside a favourable overall safety profile. Key secondary assessments confirmed that bone health was maintained in those who transitioned to efzimfotase alfa, with an observed median difference in RGI-C score of 0 between the efzimfotase alfa and Strensiq groups, and comparable Rickets Severity Score medians across both arms.

Complete findings from the HICKORY Phase III trial, which is examining adolescents and adults aged 12 and above with hypophosphatasia who have not previously received Strensiq, will be presented at a future medical meeting.

“Underlying alkaline phosphatase deficiency in HPP can lead to severe, progressive bone, neurological and functional symptoms in children with detrimental impact to physical and social-emotional wellbeing during a critical stage of development. These positive results, including a statistically significant improvement in bone health and meaningful benefit in physical function, represent a clinically important advancement for children living with this lifelong disease,” said Jill Simmons, MD, Director of the Program for Pediatric Metabolic Bone Disorders at Vanderbilt Health, Interim Director of Pediatric Endocrinology and Professor of Pediatric Endocrinology at Vanderbilt University, and principal investigator for the CHESTNUT trial.

“The efzimfotase alfa Phase III clinical programme represents the largest and most diverse investigation of HPP to date, spanning a broad patient population with a wide range of disease manifestations. By addressing the root cause of HPP, alkaline phosphatase deficiency, efzimfotase alfa has the potential to meaningfully improve outcomes with a convenient, self-administered option for the HPP patient community,” said Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, AstraZeneca Rare Disease.

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Related Topics and Keywords

Efzimfotase alfa, hypophosphatasia, MULBERRY Phase III trial