Positive Phase III data from the MULBERRY trial indicate that efzimfotase alfa produced a statistically significant and clinically meaningful improvement in bone health in children aged 2 to under 12 years with hypophosphatasia (HPP).
In the trial, children treated with efzimfotase alfa (ALXN1850), an investigational enzyme replacement therapy, achieved an observed median RGI-C Score of 1.67 at week 25, compared with 0 in the placebo group, yielding a median difference of 1.67.
The study also met its key secondary endpoint for bone health. On the Rickets Severity Score (RSS), efzimfotase alfa showed a statistically significant improvement at week 25, with a median change of –1.00 versus 0 for placebo, a median difference of –1.00.
Functional and quality-of-life measures also showed encouraging signals. On the Paediatric Outcomes Data Collection Instrument (PODCI) Global Function normative score, the treatment group demonstrated a nominally significant median difference of 9.0.
In the Six-Minute Walk Test (6MWT), patients showed a median improvement of 34.5 meters compared with placebo, though this did not reach statistical significance.
In the CHESTNUT trial, efzimfotase alfa showed a similar incidence of treatment-emergent adverse events at week 25 in children who switched from Strensiq (90.5%) compared with those who remained on Strensiq (86.4%), with a favourable safety profile.
Bone health outcomes were maintained in children transitioning to efzimfotase alfa, including a median RGI-C score difference of 0 versus Strensiq and a median RSS difference of 0 versus –0.08.
Jill Simmons, principal investigator for CHESTNUT, said: "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.”
Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety at Alexion, AstraZeneca Rare Disease, said: “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.”
